Spolupracovali sme na publikáciach
2025
18.
Horti-Oravecz, Klaudia; Bozsik, Anikó; Pócza, Tímea; Vereczkey, Ildikó; Strausz, Tamás; Tóth, Erika; Sedlackova, Tatiana; Rusnakova, Diana; Szemes, Tomas; Likó, István; Oláh, Edit; Butz, Henriett; Patócs, Attila; Papp, János; Grolmusz, Vince Kornél
Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome Journal Article
V: npj Genomic Medicine, 10 (1), 2025, ISSN: 20567944.
Abstrakt | Linky | BibTeX | Značky: Genetic testing, Oncology
@article{Horti-Oravecz2025,
title = {Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome},
author = {Klaudia Horti-Oravecz and Anikó Bozsik and Tímea Pócza and Ildikó Vereczkey and Tamás Strausz and Erika Tóth and Tatiana Sedlackova and Diana Rusnakova and Tomas Szemes and István Likó and Edit Oláh and Henriett Butz and Attila Patócs and János Papp and Vince Kornél Grolmusz},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85218225344&doi=10.1038%2fs41525-025-00461-z&partnerID=40&md5=f46292994e758b7a6c8b581f44c1938a},
doi = {10.1038/s41525-025-00461-z},
issn = {20567944},
year = {2025},
date = {2025-01-01},
urldate = {2025-01-01},
journal = {npj Genomic Medicine},
volume = {10},
number = {1},
publisher = {Nature Research},
abstract = {Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its’ pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS. © The Author(s) 2025.},
keywords = {Genetic testing, Oncology},
pubstate = {published},
tppubtype = {article}
}
Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its’ pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS. © The Author(s) 2025.
2024
17.
Lukacova, E.; Hanzlikova, Z.; Podlesnyi, P.; Sedlackova, T.; Szemes, T.; Grendar, M.; Samec, M.; Hurtova, T.; Malicherova, B.; Leskova, K.; Budis, J.; Burjanivova, T.
Novel liquid biopsy CNV biomarkers in malignant melanoma Journal Article
V: Scientific Reports, 14 (1), 2024, ISSN: 20452322.
Abstrakt | Linky | BibTeX | Značky: Liquid biopsy, Oncology
@article{Lukacova2024,
title = {Novel liquid biopsy CNV biomarkers in malignant melanoma},
author = {E. Lukacova and Z. Hanzlikova and P. Podlesnyi and T. Sedlackova and T. Szemes and M. Grendar and M. Samec and T. Hurtova and B. Malicherova and K. Leskova and J. Budis and T. Burjanivova},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197798133&doi=10.1038%2fs41598-024-65928-y&partnerID=40&md5=5640df31219fd97cf224ab24649c395c},
doi = {10.1038/s41598-024-65928-y},
issn = {20452322},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Scientific Reports},
volume = {14},
number = {1},
publisher = {Nature Research},
abstract = {Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis. © The Author(s) 2024.},
keywords = {Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis. © The Author(s) 2024.
16.
Rendek, T.; Pos, O.; Duranova, T.; Saade, R.; Budis, J.; Repiska, V.; Szemes, T.
Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics Journal Article
V: Cancers, 16 (11), 2024, ISSN: 20726694.
Abstrakt | Linky | BibTeX | Značky: Cell-free nucleic acids, Liquid biopsy, Oncology, Review
@article{Rendek2024b,
title = {Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics},
author = {T. Rendek and O. Pos and T. Duranova and R. Saade and J. Budis and V. Repiska and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85195678349&doi=10.3390%2fcancers16112001&partnerID=40&md5=a00b727d255d45e6c52a69ea1697e97a},
doi = {10.3390/cancers16112001},
issn = {20726694},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Cancers},
volume = {16},
number = {11},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
abstract = {In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, and adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence of malignity regardless of its type and location while leveraging blood-based liquid biopsies as a method to obtain analytical samples. However, technical difficulties, costs and challenges resulting from biological variations, tumor heterogeneity, and exogenous factors persist. This method exploits the mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, and high background noise. This review explores cfDNA methylation’s origins, means of detection, and profiling for cancer diagnostics. The critical evaluation of currently available multi-cancer early detection methods (MCEDs) as well as tests targeting single genes, emphasizing their potential and limits to refine strategies for early cancer detection, are explained. The current methodology limitations, workflows, comparisons of clinically approved liquid biopsy-based methylation tests for cancer, their utilization in companion diagnostics as well as the biological limitations of the epigenetics approach are discussed, aiming to help healthcare providers as well as researchers to orient themselves in this increasingly complex and evolving field of diagnostics. © 2024 by the authors.},
keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology, Review},
pubstate = {published},
tppubtype = {article}
}
In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, and adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence of malignity regardless of its type and location while leveraging blood-based liquid biopsies as a method to obtain analytical samples. However, technical difficulties, costs and challenges resulting from biological variations, tumor heterogeneity, and exogenous factors persist. This method exploits the mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, and high background noise. This review explores cfDNA methylation’s origins, means of detection, and profiling for cancer diagnostics. The critical evaluation of currently available multi-cancer early detection methods (MCEDs) as well as tests targeting single genes, emphasizing their potential and limits to refine strategies for early cancer detection, are explained. The current methodology limitations, workflows, comparisons of clinically approved liquid biopsy-based methylation tests for cancer, their utilization in companion diagnostics as well as the biological limitations of the epigenetics approach are discussed, aiming to help healthcare providers as well as researchers to orient themselves in this increasingly complex and evolving field of diagnostics. © 2024 by the authors.
15.
Lukáčová, E.; Pös, O.; Túryová, E.; Hurtová, T.; Hanzlíková, Z.; Szemes, T.; Burjanivová, T.
Copy number variations in malignant melanoma: genomic regions, biomarkers, and therapeutic targets Journal Article
V: Neoplasma, 71 (2), pp. 143-152, 2024, ISSN: 00282685.
Abstrakt | Linky | BibTeX | Značky: Copy number variation, Oncology
@article{Lukáčová2024143,
title = {Copy number variations in malignant melanoma: genomic regions, biomarkers, and therapeutic targets},
author = {E. Lukáčová and O. Pös and E. Túryová and T. Hurtová and Z. Hanzlíková and T. Szemes and T. Burjanivová},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85193674159&doi=10.4149%2fneo_2024_240207N58&partnerID=40&md5=eda6c5ac3bdd1a7f4c629f9b73bbaa44},
doi = {10.4149/neo_2024_240207N58},
issn = {00282685},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Neoplasma},
volume = {71},
number = {2},
pages = {143-152},
abstract = {Malignant melanoma is a skin tumor arising from melanocytes, occurring mostly in predisposed individuals. Melanomas are frequently present with copy number variations (CNVs), i.e., gains or losses of specific DNA regions that have provided immense potential for disease diagnosis and classification. The methodology of CNV detection has revolutionized in past decades, and current high throughput technologies enable us to analyze the entire spectrum of CNV alterations at the whole genome scale. Thus, identifying novel CNV biomarkers and evaluating their applicability in biomedicine are becoming increasingly important. The aim of this review was to summarize copy number changes occurring in malignant melanomas. We made an overview of specific genes and chromosomal locations affected in sporadic and familial melanoma and also of known germline alterations in melanoma-prone families. We summarized genomic regions aberrant in malignant melanoma and highlighted those frequently discussed in the literature, suggesting 7q, 11q, 12q, 9p, and 1q, but also others, as the most affected ones.},
keywords = {Copy number variation, Oncology},
pubstate = {published},
tppubtype = {article}
}
Malignant melanoma is a skin tumor arising from melanocytes, occurring mostly in predisposed individuals. Melanomas are frequently present with copy number variations (CNVs), i.e., gains or losses of specific DNA regions that have provided immense potential for disease diagnosis and classification. The methodology of CNV detection has revolutionized in past decades, and current high throughput technologies enable us to analyze the entire spectrum of CNV alterations at the whole genome scale. Thus, identifying novel CNV biomarkers and evaluating their applicability in biomedicine are becoming increasingly important. The aim of this review was to summarize copy number changes occurring in malignant melanomas. We made an overview of specific genes and chromosomal locations affected in sporadic and familial melanoma and also of known germline alterations in melanoma-prone families. We summarized genomic regions aberrant in malignant melanoma and highlighted those frequently discussed in the literature, suggesting 7q, 11q, 12q, 9p, and 1q, but also others, as the most affected ones.
14.
Rendek, T.; Saade, R.; Pos, O.; Kolnikova, G.; Urbanova, M.; Budis, J.; Mihok, L.; Tomas, M.; Szemes, T.; Repiska, V.
Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia Journal Article
V: Cancers, 16 (6), 2024, ISSN: 20726694.
Abstrakt | Linky | BibTeX | Značky: Oncology
@article{Rendek2024,
title = {Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia},
author = {T. Rendek and R. Saade and O. Pos and G. Kolnikova and M. Urbanova and J. Budis and L. Mihok and M. Tomas and T. Szemes and V. Repiska},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188716763&doi=10.3390%2fcancers16061128&partnerID=40&md5=6d2a917f36ffefb2b941d96e515e7a83},
doi = {10.3390/cancers16061128},
issn = {20726694},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {Cancers},
volume = {16},
number = {6},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
abstract = {Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population. © 2024 by the authors.},
keywords = {Oncology},
pubstate = {published},
tppubtype = {article}
}
Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare system this disease imposes, data on molecular analysis of biomarkers in CRC-diagnosed patients is scarce. In our study, we analyzed confirmed CRC patients from the database of the National Cancer Institute (NCI) and evaluated the presence of 4 biomarkers in tumor tissues. Altogether, 83 FFPE tumor tissues from CRC patients listed in the NCI database were analyzed for microsatellite instability status, presence of BRAF and KRAS/NRAS mutations, and neoplastic cell percentage in tissue samples. We identified 4 MSI-high samples, 39 KRAS/NRAS mutations, and 5 BRAF p.V600E mutations, with one case of coexistence of all three markers in a single tumor sample. We also evaluated possible relationships between biomarkers, their coexistence, and the age and sex of the studied population. © 2024 by the authors.
2023
13.
Styk, J.; Pös, Z.; Pös, O.; Radvanszky, J.; Turnova, E. H.; Buglyó, G.; Klimova, D.; Budis, J.; Repiska, V.; Nagy, B.; Szemes, T.
Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook Journal Article
V: EPMA Journal, 2023, ISSN: 18785077.
Abstrakt | Linky | BibTeX | Značky: Liquid biopsy, Oncology
@article{Styk2023,
title = {Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook},
author = {J. Styk and Z. Pös and O. Pös and J. Radvanszky and E. H. Turnova and G. Buglyó and D. Klimova and J. Budis and V. Repiska and B. Nagy and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146857319&doi=10.1007%2fs13167-023-00312-w&partnerID=40&md5=3b63e993459e80e985772551f60bbc4e},
doi = {10.1007/s13167-023-00312-w},
issn = {18785077},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {EPMA Journal},
publisher = {Springer Science and Business Media Deutschland GmbH},
abstract = {A form of genomic alteration called microsatellite instability (MSI) occurs in a class of tandem repeats (TRs) called microsatellites (MSs) or short tandem repeats (STRs) due to the failure of a post-replicative DNA mismatch repair (MMR) system. Traditionally, the strategies for determining MSI events have been low-throughput procedures that typically require assessment of tumours as well as healthy samples. On the other hand, recent large-scale pan-tumour studies have consistently highlighted the potential of massively parallel sequencing (MPS) on the MSI scale. As a result of recent innovations, minimally invasive methods show a high potential to be integrated into the clinical routine and delivery of adapted medical care to all patients. Along with advances in sequencing technologies and their ever-increasing cost-effectiveness, they may bring about a new era of Predictive, Preventive and Personalised Medicine (3PM). In this paper, we offered a comprehensive analysis of high-throughput strategies and computational tools for the calling and assessment of MSI events, including whole-genome, whole-exome and targeted sequencing approaches. We also discussed in detail the detection of MSI status by current MPS blood-based methods and we hypothesised how they may contribute to the shift from conventional medicine to predictive diagnosis, targeted prevention and personalised medical services. Increasing the efficacy of patient stratification based on MSI status is crucial for tailored decision-making. Contextually, this paper highlights drawbacks both at the technical level and those embedded deeper in cellular/molecular processes and future applications in routine clinical testing. © 2023, The Author(s).},
keywords = {Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
A form of genomic alteration called microsatellite instability (MSI) occurs in a class of tandem repeats (TRs) called microsatellites (MSs) or short tandem repeats (STRs) due to the failure of a post-replicative DNA mismatch repair (MMR) system. Traditionally, the strategies for determining MSI events have been low-throughput procedures that typically require assessment of tumours as well as healthy samples. On the other hand, recent large-scale pan-tumour studies have consistently highlighted the potential of massively parallel sequencing (MPS) on the MSI scale. As a result of recent innovations, minimally invasive methods show a high potential to be integrated into the clinical routine and delivery of adapted medical care to all patients. Along with advances in sequencing technologies and their ever-increasing cost-effectiveness, they may bring about a new era of Predictive, Preventive and Personalised Medicine (3PM). In this paper, we offered a comprehensive analysis of high-throughput strategies and computational tools for the calling and assessment of MSI events, including whole-genome, whole-exome and targeted sequencing approaches. We also discussed in detail the detection of MSI status by current MPS blood-based methods and we hypothesised how they may contribute to the shift from conventional medicine to predictive diagnosis, targeted prevention and personalised medical services. Increasing the efficacy of patient stratification based on MSI status is crucial for tailored decision-making. Contextually, this paper highlights drawbacks both at the technical level and those embedded deeper in cellular/molecular processes and future applications in routine clinical testing. © 2023, The Author(s).
12.
Pös, O.; Styk, J.; Buglyó, G.; Zeman, M.; Lukyova, L.; Bernatova, K.; Turnova, E. Hrckova; Rendek, T.; Csók, Á.; Repiska, V.; Nagy, B.; Szemes, T.
Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer Journal Article
V: International Journal of Molecular Sciences, 24 (13), 2023, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Gut microbiome, Oncology
@article{Pös2023,
title = {Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer},
author = {O. Pös and J. Styk and G. Buglyó and M. Zeman and L. Lukyova and K. Bernatova and E. Hrckova Turnova and T. Rendek and Á. Csók and V. Repiska and B. Nagy and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164844125&doi=10.3390%2fijms241310520&partnerID=40&md5=7a3be1fd203bc9e0cf04f84a8bbfe4de},
doi = {10.3390/ijms241310520},
issn = {16616596},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {International Journal of Molecular Sciences},
volume = {24},
number = {13},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
abstract = {Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile. © 2023 by the authors.},
keywords = {Gut microbiome, Oncology},
pubstate = {published},
tppubtype = {article}
}
Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile. © 2023 by the authors.
11.
Klimova, D.; Jakubechova, J.; Altanerova, U.; Nicodemou, A.; Styk, J.; Szemes, T.; Repiska, V.; Altaner, C.
V: Molecular and Cellular Probes, 67 , 2023, ISSN: 08908508.
Abstrakt | Linky | BibTeX | Značky: Oncology
@article{Klimova2023,
title = {Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as a cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro},
author = {D. Klimova and J. Jakubechova and U. Altanerova and A. Nicodemou and J. Styk and T. Szemes and V. Repiska and C. Altaner},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147104802&doi=10.1016%2fj.mcp.2023.101894&partnerID=40&md5=bd0eb370c53359ac5e12f26b2fbea314},
doi = {10.1016/j.mcp.2023.101894},
issn = {08908508},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Molecular and Cellular Probes},
volume = {67},
publisher = {Academic Press},
abstract = {Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system. © 2023 The Author(s)},
keywords = {Oncology},
pubstate = {published},
tppubtype = {article}
}
Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system. © 2023 The Author(s)
10.
Holesova, Z.; Krasnicanova, L.; Saade, R.; Pös, O.; Budis, J.; Gazdarica, J.; Repiska, V.; Szemes, T.
Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies Journal Article
V: Genes, 14 (3), 2023, ISSN: 20734425.
Abstrakt | Linky | BibTeX | Značky: Liquid biopsy, Oncology
@article{Holesova2023,
title = {Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies},
author = {Z. Holesova and L. Krasnicanova and R. Saade and O. Pös and J. Budis and J. Gazdarica and V. Repiska and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85151112952&doi=10.3390%2fgenes14030715&partnerID=40&md5=d89df2608717b306d353873f39018ecb},
doi = {10.3390/genes14030715},
issn = {20734425},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Genes},
volume = {14},
number = {3},
publisher = {MDPI},
abstract = {Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. © 2023 by the authors.},
keywords = {Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field. © 2023 by the authors.
2022
9.
Soltész, B.; Pös, O.; Wlachovska, Z.; Budis, J.; Hekel, R.; Strieskova, L.; Liptak, J. B.; Krampl, W.; Styk, J.; Németh, N.; Keserű, J. S.; Jenei, A.; Buglyó, G.; Klekner, Á.; Nagy, B.; Szemes, T.
Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients Journal Article
V: Molecular and Cellular Probes, 66 , 2022, ISSN: 08908508.
Abstrakt | Linky | BibTeX | Značky: Copy number variation, Mitochondria, Oncology
@article{Soltész2022b,
title = {Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients},
author = {B. Soltész and O. Pös and Z. Wlachovska and J. Budis and R. Hekel and L. Strieskova and J. B. Liptak and W. Krampl and J. Styk and N. Németh and J. S. Keserű and A. Jenei and G. Buglyó and Á. Klekner and B. Nagy and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142723801&doi=10.1016%2fj.mcp.2022.101875&partnerID=40&md5=cfe8239029a20ab89e08e1321a98c75e},
doi = {10.1016/j.mcp.2022.101875},
issn = {08908508},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Molecular and Cellular Probes},
volume = {66},
publisher = {Academic Press},
abstract = {Glioblastoma is the most common malignant tumor of the central nervous system (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial DNA may serve as biomarkers. As the brain is difficult to access, analysis of mitochondria directly from the brain tissue represents a challenge. Exosome analysis is an alternative (still poorly explored) approach to investigate molecular changes in CNS tumors. We analyzed brain tissue DNA and plasma-derived exosomal DNA (exoDNA) of 44 glioblastoma patients and 40 control individuals. Quantitative real-time PCR was performed to determine mtDNA copy numbers and the Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis of data. Subsequently, sequencing libraries were prepared and sequenced on the MiSeq platform to identify mtDNA point mutations. Tissue mtDNA copy number was different among controls and patients in multiple comparisons. A similar tendency was detected in exosomes. Based on NGS analysis, several mtDNA point mutations showed slightly different frequencies between cases and controls, but the clinical relevance of these observations is difficult to assess and likely less than that of overall mtDNA copy number changes. Allele frequencies of variants were used to determine the level of heteroplasmy (found to be higher in exo-mtDNA of control individuals). Despite the suggested potential, the use of such biomarkers for the screening and/or diagnosis of glioblastomas is still limited, thus further studies are needed. © 2022},
keywords = {Copy number variation, Mitochondria, Oncology},
pubstate = {published},
tppubtype = {article}
}
Glioblastoma is the most common malignant tumor of the central nervous system (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial DNA may serve as biomarkers. As the brain is difficult to access, analysis of mitochondria directly from the brain tissue represents a challenge. Exosome analysis is an alternative (still poorly explored) approach to investigate molecular changes in CNS tumors. We analyzed brain tissue DNA and plasma-derived exosomal DNA (exoDNA) of 44 glioblastoma patients and 40 control individuals. Quantitative real-time PCR was performed to determine mtDNA copy numbers and the Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis of data. Subsequently, sequencing libraries were prepared and sequenced on the MiSeq platform to identify mtDNA point mutations. Tissue mtDNA copy number was different among controls and patients in multiple comparisons. A similar tendency was detected in exosomes. Based on NGS analysis, several mtDNA point mutations showed slightly different frequencies between cases and controls, but the clinical relevance of these observations is difficult to assess and likely less than that of overall mtDNA copy number changes. Allele frequencies of variants were used to determine the level of heteroplasmy (found to be higher in exo-mtDNA of control individuals). Despite the suggested potential, the use of such biomarkers for the screening and/or diagnosis of glioblastomas is still limited, thus further studies are needed. © 2022
8.
Styk, J.; Buglyó, G.; Pös, O.; Csók, Á.; Soltész, B.; Lukasz, P.; Repiská, V.; Nagy, B.; Szemes, T.
Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer Journal Article
V: Cancers, 14 (15), 2022, ISSN: 20726694.
Abstrakt | Linky | BibTeX | Značky: Cell-free nucleic acids, Liquid biopsy, Oncology
@article{Styk2022,
title = {Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer},
author = {J. Styk and G. Buglyó and O. Pös and Á. Csók and B. Soltész and P. Lukasz and V. Repiská and B. Nagy and T. Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136586949&doi=10.3390%2fcancers14153712&partnerID=40&md5=c1693e930ca57ea69fb9f5147e1de219},
doi = {10.3390/cancers14153712},
issn = {20726694},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Cancers},
volume = {14},
number = {15},
publisher = {MDPI},
abstract = {Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management. © 2022 by the authors.},
keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Colorectal cancer (CRC) is the 3rd most common malignant neoplasm worldwide, with more than two million new cases diagnosed yearly. Despite increasing efforts in screening, many cases are still diagnosed at a late stage, when mortality is high. This paper briefly reviews known genetic causes of CRC (distinguishing between sporadic and familial forms) and discusses potential and confirmed nucleic acid biomarkers obtainable from liquid biopsies, classified by their molecular features, focusing on clinical relevance. We comment on advantageous aspects such as better patient compliance due to blood sampling being minimally invasive, the possibility to monitor mutation characteristics of sporadic and hereditary CRC in a disease showing genetic heterogeneity, and using up- or down-regulated circulating RNA markers to reveal metastasis or disease recurrence. Current difficulties and thoughts on some possible future directions are also discussed. We explore current evidence in the field pointing towards the introduction of personalized CRC management. © 2022 by the authors.
7.
Buglyó, G.; Styk, J.; Pös, O.; Csók, Á.; Repiska, V.; Soltész, B.; Szemes, T.; Nagy, B.
Liquid Biopsy as a Source of Nucleic Acid Biomarkers in the Diagnosis and Management of Lynch Syndrome Journal Article
V: International Journal of Molecular Sciences, 23 (8), 2022, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Liquid biopsy, Oncology
@article{Buglyó2022,
title = {Liquid Biopsy as a Source of Nucleic Acid Biomarkers in the Diagnosis and Management of Lynch Syndrome},
author = {G. Buglyó and J. Styk and O. Pös and Á. Csók and V. Repiska and B. Soltész and T. Szemes and B. Nagy},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128130388&doi=10.3390%2fijms23084284&partnerID=40&md5=b115dc9efc5482690694163145c4f23e},
doi = {10.3390/ijms23084284},
issn = {16616596},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {International Journal of Molecular Sciences},
volume = {23},
number = {8},
publisher = {MDPI},
abstract = {Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition disorder, which may manifest as colorectal cancer (CRC), endometrial cancer (EC) or other malignancies of the gastrointestinal and genitourinary tract as well as the skin and brain. Its genetic cause is a defect in one of the four key DNA mismatch repair (MMR) loci. Testing of patients at risk is currently based on the absence of MMR protein staining and detection of mutations in cancer tissue and the germline, microsatellite instability (MSI) and the hypermethylated state of the MLH1 promoter. If LS is shown to have caused CRC, lifetime follow-up with regular screening (most importantly, colonoscopy) is required. In recent years, DNA and RNA markers extracted from liquid biopsies have found some use in the clinical diagnosis of LS. They have the potential to greatly enhance the efficiency of the follow-up process by making it minimally invasive, reproducible, and time effective. Here, we review markers reported in the literature and their current clinical applications, and we comment on possible future directions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Lynch syndrome (LS) is an autosomal dominant inherited cancer predisposition disorder, which may manifest as colorectal cancer (CRC), endometrial cancer (EC) or other malignancies of the gastrointestinal and genitourinary tract as well as the skin and brain. Its genetic cause is a defect in one of the four key DNA mismatch repair (MMR) loci. Testing of patients at risk is currently based on the absence of MMR protein staining and detection of mutations in cancer tissue and the germline, microsatellite instability (MSI) and the hypermethylated state of the MLH1 promoter. If LS is shown to have caused CRC, lifetime follow-up with regular screening (most importantly, colonoscopy) is required. In recent years, DNA and RNA markers extracted from liquid biopsies have found some use in the clinical diagnosis of LS. They have the potential to greatly enhance the efficiency of the follow-up process by making it minimally invasive, reproducible, and time effective. Here, we review markers reported in the literature and their current clinical applications, and we comment on possible future directions. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
6.
Soltész, B.; Buglyó, G.; Németh, N.; Szilágyi, M.; Pös, O.; Szemes, T.; Balogh, I.; Nagy, B.
The role of exosomes in cancer progression Journal Article
V: International Journal of Molecular Sciences, 23 (1), 2022, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Cell-free nucleic acids, Liquid biopsy, Oncology
@article{Soltész2022,
title = {The role of exosomes in cancer progression},
author = {B. Soltész and G. Buglyó and N. Németh and M. Szilágyi and O. Pös and T. Szemes and I. Balogh and B. Nagy},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85121366077&doi=10.3390%2fijms23010008&partnerID=40&md5=a6c0cdd2a0624326aa4378c4af43611b},
doi = {10.3390/ijms23010008},
issn = {16616596},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {International Journal of Molecular Sciences},
volume = {23},
number = {1},
publisher = {MDPI},
abstract = {Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non‐invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell‐to‐cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next‐generation treatment of cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Cell-free nucleic acids, Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non‐invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell‐to‐cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next‐generation treatment of cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
2021
5.
Forgacova, N; Gazdarica, J; Budis, J; Radvanszky, J; Szemes, T
V: Oncology Letters, 22 (5), 2021, ISSN: 17921074.
Abstrakt | Linky | BibTeX | Značky: Non-invasive prenatal testing, Oncology, Population study
@article{Forgacova2021,
title = {Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with Colorectal Cancer and Lynch Syndrome},
author = {N Forgacova and J Gazdarica and J Budis and J Radvanszky and T Szemes},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85115197955&doi=10.3892%2fol.2021.13040&partnerID=40&md5=2e80f1d2538655ce09382de2cd0b3e20},
doi = {10.3892/ol.2021.13040},
issn = {17921074},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Oncology Letters},
volume = {22},
number = {5},
publisher = {Spandidos Publications},
abstract = {In our previous work, genomic data generated through non‑invasive prenatal testing (NIPT) based on low‑coverage massively parallel whole‑genome sequencing of totalplasmaDNAofpregnantwomeninSlovakiawasdescribed as a valuable source of population specific data. In the present study, these data were used to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, variants were interpreted, functional consequences were searched for and clinical significance of variants was investigated using publicly available databases. Although the present study did not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, significant differences were observed in the allelic frequency of risk CRC variants previously reported in genome‑wide association studies and common variants located in genes associated with LS. As Slovakia is one of the leading countries with the highest incidence of CRC among male patients in the world, there is a need for studies dedicated to investigating the cause of such a high incidence of CRC in Slovakia. The present study also assumed that extensive cross‑country data aggregation of NIPT results would represent an unprecedented source of information concerning human genome variation in cancer research. © 2021 Spandidos Publications. All rights reserved.},
keywords = {Non-invasive prenatal testing, Oncology, Population study},
pubstate = {published},
tppubtype = {article}
}
In our previous work, genomic data generated through non‑invasive prenatal testing (NIPT) based on low‑coverage massively parallel whole‑genome sequencing of totalplasmaDNAofpregnantwomeninSlovakiawasdescribed as a valuable source of population specific data. In the present study, these data were used to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, variants were interpreted, functional consequences were searched for and clinical significance of variants was investigated using publicly available databases. Although the present study did not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, significant differences were observed in the allelic frequency of risk CRC variants previously reported in genome‑wide association studies and common variants located in genes associated with LS. As Slovakia is one of the leading countries with the highest incidence of CRC among male patients in the world, there is a need for studies dedicated to investigating the cause of such a high incidence of CRC in Slovakia. The present study also assumed that extensive cross‑country data aggregation of NIPT results would represent an unprecedented source of information concerning human genome variation in cancer research. © 2021 Spandidos Publications. All rights reserved.
4.
Radvanszky, J; Hyblova, M; Radvanska, E; Spalek, P; Valachova, A; Magyarova, G; Bognar, C; Polak, E; Szemes, T; Kadasi, L
Characterisation of non-pathogenic premutation-range myotonic dystrophy type 2 alleles Journal Article
V: Journal of Clinical Medicine, 10 (17), 2021, ISSN: 20770383.
Abstrakt | Linky | BibTeX | Značky: Non-invasive prenatal testing, Oncology, Single nucleotide variants
@article{Radvanszky2021,
title = {Characterisation of non-pathogenic premutation-range myotonic dystrophy type 2 alleles},
author = {J Radvanszky and M Hyblova and E Radvanska and P Spalek and A Valachova and G Magyarova and C Bognar and E Polak and T Szemes and L Kadasi},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114043590&doi=10.3390%2fjcm10173934&partnerID=40&md5=57bc1cfc4be446edf6fbfea3c9ad284a},
doi = {10.3390/jcm10173934},
issn = {20770383},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Journal of Clinical Medicine},
volume = {10},
number = {17},
publisher = {MDPI},
abstract = {Myotonic dystrophy type 2 (DM2) is caused by expansion of a (CCTG)n repeat in the cellular retroviral nucleic acid-binding protein (CNBP) gene. The sequence of the repeat is most commonly interrupted and is stably inherited in the general population. Although expanded alleles, premutation range and, in rare cases, also non-disease associated alleles containing uninterrupted CCTG tracts have been described, the threshold between these categories is poorly characterised. Here, we describe four families with members reporting neuromuscular complaints, in whom we identified altogether nine ambiguous CNBP alleles containing uninterrupted CCTG repeats in the range between 32 and 42 repeats. While these grey-zone alleles are most likely not pathogenic themselves, since other pathogenic mutations were identified and particular family structures did not support their pathogenic role, they were found to be unstable during intergenerational transmission. On the other hand, there was no observable general microsatellite instability in the genome of the carriers of these alleles. Our results further refine the division of CNBP CCTG repeat alleles into two major groups, i.e., interrupted and uninterrupted alleles. Both interrupted and uninterrupted alleles with up to approximately 30 CCTG repeats were shown to be generally stable during intergenerational transmission, while intergenerational as well as somatic instability seems to gradually increase in uninterrupted alleles with tract length growing above this threshold. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Non-invasive prenatal testing, Oncology, Single nucleotide variants},
pubstate = {published},
tppubtype = {article}
}
Myotonic dystrophy type 2 (DM2) is caused by expansion of a (CCTG)n repeat in the cellular retroviral nucleic acid-binding protein (CNBP) gene. The sequence of the repeat is most commonly interrupted and is stably inherited in the general population. Although expanded alleles, premutation range and, in rare cases, also non-disease associated alleles containing uninterrupted CCTG tracts have been described, the threshold between these categories is poorly characterised. Here, we describe four families with members reporting neuromuscular complaints, in whom we identified altogether nine ambiguous CNBP alleles containing uninterrupted CCTG repeats in the range between 32 and 42 repeats. While these grey-zone alleles are most likely not pathogenic themselves, since other pathogenic mutations were identified and particular family structures did not support their pathogenic role, they were found to be unstable during intergenerational transmission. On the other hand, there was no observable general microsatellite instability in the genome of the carriers of these alleles. Our results further refine the division of CNBP CCTG repeat alleles into two major groups, i.e., interrupted and uninterrupted alleles. Both interrupted and uninterrupted alleles with up to approximately 30 CCTG repeats were shown to be generally stable during intergenerational transmission, while intergenerational as well as somatic instability seems to gradually increase in uninterrupted alleles with tract length growing above this threshold. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
2020
3.
Smolkova, B; Cierna, Z; Kalavska, K; Miklikova, S; Plava, J; Minarik, G; Sedlackova, T; Cholujova, D; Gronesova, P; Cihova, M; Majerova, K; Karaba, M; Benca, J; Pindak, D; Mardiak, J; Mego, M
V: International Journal of Molecular Sciences, 21 (24), pp. 1-16, 2020, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Body fluids, Circulating tumor cells, Liquid biopsy, Oncology
@article{Smolkova20201,
title = {Increased stromal infiltrating lymphocytes are associated with the risk of disease progression in mesenchymal circulating tumor cell-positive primary breast cancer patients},
author = {B Smolkova and Z Cierna and K Kalavska and S Miklikova and J Plava and G Minarik and T Sedlackova and D Cholujova and P Gronesova and M Cihova and K Majerova and M Karaba and J Benca and D Pindak and J Mardiak and M Mego},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097678410&doi=10.3390%2fijms21249460&partnerID=40&md5=8dd0aa352be241f64188de23774ac3c4},
doi = {10.3390/ijms21249460},
issn = {16616596},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {24},
pages = {1-16},
publisher = {MDPI AG},
abstract = {Circulating tumor cells (CTCs) and the immune infiltration of tumors are closely related to clinical outcomes. This study aimed to verify the influence of stromal lymphocyte infiltration and the immune context of tumor microenvironment on the hematogenous spread and prognosis of 282 chemotherapy naïve primary BC patients. To detect the presence of mesenchymal CTCs, RNA extracted from CD45-depleted peripheral blood was interrogated for the expression of mesenchymal gene transcripts. Tumor-infiltrating lymphocytes (TILs) were detected in the stromal areas by immunohistochemistry, using CD3, CD8, and CD45RO antibodies. The concentrations of 51 plasma cytokines were measured by multiplex bead arrays. TILs infiltration in mesenchymal CTC-positive patients significantly decreased their progression-free survival (HR = 4.88, 95% CI 2.30–10.37, p < 0.001 for CD3high; HR = 6.17, 95% CI 2.75–13.80, p < 0.001 for CD8high; HR = 6.93, 95% CI 2.86–16.81, p < 0.001 for CD45ROhigh). Moreover, the combination of elevated plasma concentrations of transforming growth factor beta-3 (cut-off 662 pg/mL), decreased monocyte chemotactic protein-3 (cut-off 52.5 pg/mL) and interleukin-15 (cut-off 17.1 pg/mL) significantly increased the risk of disease recurrence (HR = 4.838, 95% CI 2.048–11.427, p < 0.001). Our results suggest a strong impact of the immune tumor microenvironment on BC progression, especially through influencing the dissemination and survival of more aggressive, mesenchymal CTC subtypes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Body fluids, Circulating tumor cells, Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Circulating tumor cells (CTCs) and the immune infiltration of tumors are closely related to clinical outcomes. This study aimed to verify the influence of stromal lymphocyte infiltration and the immune context of tumor microenvironment on the hematogenous spread and prognosis of 282 chemotherapy naïve primary BC patients. To detect the presence of mesenchymal CTCs, RNA extracted from CD45-depleted peripheral blood was interrogated for the expression of mesenchymal gene transcripts. Tumor-infiltrating lymphocytes (TILs) were detected in the stromal areas by immunohistochemistry, using CD3, CD8, and CD45RO antibodies. The concentrations of 51 plasma cytokines were measured by multiplex bead arrays. TILs infiltration in mesenchymal CTC-positive patients significantly decreased their progression-free survival (HR = 4.88, 95% CI 2.30–10.37, p < 0.001 for CD3high; HR = 6.17, 95% CI 2.75–13.80, p < 0.001 for CD8high; HR = 6.93, 95% CI 2.86–16.81, p < 0.001 for CD45ROhigh). Moreover, the combination of elevated plasma concentrations of transforming growth factor beta-3 (cut-off 662 pg/mL), decreased monocyte chemotactic protein-3 (cut-off 52.5 pg/mL) and interleukin-15 (cut-off 17.1 pg/mL) significantly increased the risk of disease recurrence (HR = 4.838, 95% CI 2.048–11.427, p < 0.001). Our results suggest a strong impact of the immune tumor microenvironment on BC progression, especially through influencing the dissemination and survival of more aggressive, mesenchymal CTC subtypes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
2.
Soltysova, A; Sedlackova, T; Dvorska, D; Jasek, K; Baradaran, P C; Kajabova, V H; Demkova, L; Buocikova, V; Kurucova, T; Lyskova, D; Furdova, A; Minarik, G; Babal, P; Dankova, Z; Smolkova, B
Monosomy 3 influences epithelial-mesenchymal transition gene expression in uveal melanoma patients; consequences for liquid biopsy Journal Article
V: International Journal of Molecular Sciences, 21 (24), pp. 1-24, 2020, ISSN: 16616596.
Abstrakt | Linky | BibTeX | Značky: Aneuploidy, Body fluids, Circulating tumor cells, Liquid biopsy, Oncology
@article{Soltysova20201,
title = {Monosomy 3 influences epithelial-mesenchymal transition gene expression in uveal melanoma patients; consequences for liquid biopsy},
author = {A Soltysova and T Sedlackova and D Dvorska and K Jasek and P C Baradaran and V H Kajabova and L Demkova and V Buocikova and T Kurucova and D Lyskova and A Furdova and G Minarik and P Babal and Z Dankova and B Smolkova},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097833518&doi=10.3390%2fijms21249651&partnerID=40&md5=133b8d5d56ebac3bf7a09024f007273e},
doi = {10.3390/ijms21249651},
issn = {16616596},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {24},
pages = {1-24},
publisher = {MDPI AG},
abstract = {Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCβ4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},
keywords = {Aneuploidy, Body fluids, Circulating tumor cells, Liquid biopsy, Oncology},
pubstate = {published},
tppubtype = {article}
}
Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCβ4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
2013
1.
Minárik, G; Plank, L; Lasabová, Z; Szemes, T; Burjanivová, T; Szépe, P; Buzalková, V; Porubský, D; Šufliarsky, J
Spectrum of mutations in gastrointestinal stromal tumor patients - a population-based study from Slovakia Journal Article
V: APMIS, 121 (6), pp. 539-548, 2013, ISSN: 09034641.
Abstrakt | Linky | BibTeX | Značky: Oncology, Population study, Single nucleotide variants
@article{Minárik2013539,
title = {Spectrum of mutations in gastrointestinal stromal tumor patients - a population-based study from Slovakia},
author = {G Minárik and L Plank and Z Lasabová and T Szemes and T Burjanivová and P Szépe and V Buzalková and D Porubský and J Šufliarsky},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878263424&doi=10.1111%2fapm.12019&partnerID=40&md5=dbaf848510fcae4f4e67f5505c875199},
doi = {10.1111/apm.12019},
issn = {09034641},
year = {2013},
date = {2013-01-01},
journal = {APMIS},
volume = {121},
number = {6},
pages = {539-548},
abstract = {Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract and are characterized by presence of mutations in tyrosine kinases cKIT (KIT) and PDGFRα (PDGFRA). Mutations identified are highly heterogeneous, but some mutations are associated with specific clinical features of the tumor. Samples from 278 GIST patients collected during the period 2004-2011 were screened for mutations in exons 9, 11, 13, and 17 of KIT and 12, 14 and 18 of PDGFRA. Results of mutation screening were summarized and tested for possible association with clinical parameters of tumors. Mutations were identified in 83.81% of patients. Most frequent mutations were found in KIT exon 11 reaching frequency of 62.95%. Other exons contributed to the mutation pool with frequencies 8.27%, 7.55%, 2.52%, 1.44%, 1.08%, and 0.00%, in decreasing order KIT exon 9, PDGRFA exons 18 and 12, KIT exon 13, PDGFRA exon 14, and KIT exon 17. General linear model analysis showed no effect of any individual analyzed mutation on the phenotypic variables, but we confirmed association between mutations KIT exon 9 p. 503-504_dup2, and PDGFRA exon 18 p. D842V and intestinal and gastric localization of tumors. © 2012 APMIS.},
keywords = {Oncology, Population study, Single nucleotide variants},
pubstate = {published},
tppubtype = {article}
}
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract and are characterized by presence of mutations in tyrosine kinases cKIT (KIT) and PDGFRα (PDGFRA). Mutations identified are highly heterogeneous, but some mutations are associated with specific clinical features of the tumor. Samples from 278 GIST patients collected during the period 2004-2011 were screened for mutations in exons 9, 11, 13, and 17 of KIT and 12, 14 and 18 of PDGFRA. Results of mutation screening were summarized and tested for possible association with clinical parameters of tumors. Mutations were identified in 83.81% of patients. Most frequent mutations were found in KIT exon 11 reaching frequency of 62.95%. Other exons contributed to the mutation pool with frequencies 8.27%, 7.55%, 2.52%, 1.44%, 1.08%, and 0.00%, in decreasing order KIT exon 9, PDGRFA exons 18 and 12, KIT exon 13, PDGFRA exon 14, and KIT exon 17. General linear model analysis showed no effect of any individual analyzed mutation on the phenotypic variables, but we confirmed association between mutations KIT exon 9 p. 503-504_dup2, and PDGFRA exon 18 p. D842V and intestinal and gastric localization of tumors. © 2012 APMIS.