Marianna Borecká
A5060540331- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Nutrition, Genetics, and Disease
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Genetics, Bioinformatics, and Biomedical Research
- Ovarian cancer diagnosis and treatment
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Sperm and Testicular Function
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Childhood Cancer Survivors' Quality of Life
- Neuroendocrine Tumor Research Advances
- Male Breast Health Studies
- CRISPR and Genetic Engineering
- Ethics and Legal Issues in Pediatric Healthcare
- Reproductive Biology and Fertility
- Advanced Breast Cancer Therapies
- RNA and protein synthesis mechanisms
- Pancreatic function and diabetes
Charles University
2016-2024
General University Hospital in Prague
2020-2024
Germline mutations in checkpoint kinase 2 ( CHEK2 ), a multiple cancer‐predisposing gene, increase breast cancer (BC) risk; however, risk estimates differ substantially published studies. We analyzed germline variants 1,928 high‐risk Czech breast/ovarian (BC/OC) patients and 3,360 population‐matched controls (PMCs). For functional classification of VUS, we developed complementation assay human nontransformed RPE1‐ ‐knockout cells quantifying CHK2‐specific phosphorylation endogenous protein...
Ovarian cancer (OC) is the deadliest gynecologic malignancy with a substantial proportion of hereditary cases and frequent association breast (BC). Genetic testing facilitates treatment preventive strategies reducing OC mortality in mutation carriers. However, prevalence germline mutations varies among populations many rarely mutated predisposition genes remain to be identified. We aimed analyze 219 1333 Czech patients 2278 population-matched controls using next-generation sequencing....
Background Carriers of mutations in hereditary cancer predisposition genes represent a small but clinically important subgroup oncology patients. The identification causal germline determines follow-up management, treatment options and genetic counselling patients' families. Targeted next-generation sequencing-based analyses using cancer-specific panels high-risk individuals have been rapidly adopted by diagnostic laboratories. While the use diagnosis-specific is straightforward typical...
Germline CHEK2 pathogenic variants confer an increased risk of female breast cancer (FBC). Here we describe a recurrent germline intronic variant c.1009-118_1009-87delinsC, which showed splice acceptor shift in RNA analysis, introducing premature stop codon (p.Tyr337PhefsTer37). The was found 21/10,204 (0.21%) Czech FBC patients compared to 1/3250 (0.03%) controls (p = 0.04) and 4/3639 (0.11%) from independent German dataset. In addition, this 5/2966 (0.17%) (but none the 443 German) ovarian...
Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, the significance of variables influencing sporadic BC is not established patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed effect clinicopathological characteristics on (disease-free survival [DFS] disease-specific [DSS]) carriers. We enrolled 234 899 non-carriers, whom 191 680 complete data, were available for analyses. found that ER-positive...
Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. The present study aimed to determine frequency of germline pathogenic variants (PV) patients with EC. In this multicenter retrospective cohort study, genetic testing (GGT) was performed 527 EC using a next generation sequencing panel targeting 226 genes, including 5 Lynch syndrome (LS) and 14 hereditary breast ovarian (HBOC) predisposition 207 candidate genes. Gene-level risks were calculated 1,662...
(1) Background: The proportion and spectrum of germline pathogenic variants (PV) associated with an increased risk for pancreatic ductal adenocarcinoma (PDAC) varies among populations. (2) Methods: We analyzed 72 Belgian 226 Czech PDAC patients by multigene panel testing. prevalence in relation to personal/family cancer history were evaluated. risks calculated using both gnomAD-NFE population-matched controls. (3) Results: In 35/298 (11.7%) a PV established PDAC-predisposition gene was...
The widespread use of next generation sequencing for clinical testing is detecting an escalating number variants in noncoding regions the genome. significance majority these currently unknown, which presents a significant challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by ENIGMA consortium sequence 5′ BC susceptibility genes BRCA1 and BRCA2, identified 141 rare with global minor allele frequency < 0.01, 76 not been reported previously....
Abstract Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in exon 6 of PPM1D result production a highly stable, C-terminally truncated PPM1D. These gain-of-function mutations are present various human cancers but their role tumorigenesis remains unresolved. Here we show that impairs activation cycle checkpoints non-transformed RPE cells allows...
Hepatocellular carcinoma (HCC) mainly stems from liver cirrhosis and its genetic predisposition is believed to be rare. However, two recent studies describe pathogenic/likely pathogenic germline variants (PV) in cancer-predisposition genes (CPG). As the risk of de novo tumors might increased PV carriers, especially immunosuppressed patients after a transplantation, we analyzed prevalence CPG HCC considered for transplantation. Using panel NGS targeting 226 CPGs, DNA 334 Czech 1662...
The polygenic risk score (PRS) allows the quantification of effect many low-penetrance alleles on breast cancer (BC). This study aimed to evaluate performance two sets comprising 77 or 313 loci (PRS77 and PRS313) in patients with BC Czech population.
Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes (BRCA1/FANCS, BRCA2/FANCD1, PALB2/FANCN, BRIP1/FANCJ, and RAD51C/FANCO) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, but the role GPVs 17 other FA remains unclear.
Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI
SouhrnVýchodiska: Gen PALB2 (FANCN) kóduje DNA reparační protein, který byl objeven jako součást endogenního multiproteinového komplexu BRCA2.Společně s proteiny BRCA1 a BRCA2 se funkčně podílí na opravách dvouřetězcových zlomů DNA.Dědičné mutace
Východiska: Dědičné mutace v genu CHEK2 kódujícím CHK2 proteinkinázu způsobují středně zvýšené riziko vzniku karcinomu prsu (breast cancer -BC) a dalších nádorových onemocnění.Vysoká populační variabilita mutací výskyt vzácných missense variant nejasného významu (variants of unknown clinical significance -VUS) komplikuje odhad rizika onemocnění u nosičů germinálních variant.Soubor pacientů metody: Mutační analýzu CHEK2, vč.analýzy velkých přestaveb, jsme provedli 1 526 vysoce rizikových...
The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors pancreatic ductal adenocarcinoma (PDAC) with regard the germline genetic background.A total 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 analyzed. Of 22 surviving for >5 years, six went on develop SMNs. A analysis 219 hereditary cancer-predisposition candidate genes performed by targeted next-generation sequencing DNA from 20 these...
Male breast cancer (mBC) is a rare diagnosis that constitutes less than 1 % of all cases globally. Genetic factors play an important role in the mBC risk. Germline pathogenic variants (PVs) predisposition genes could be identified about 15 cases. We performed germline genetic testing 248 Czech patients and 3,626 non-cancer male controls using next-generation sequencing by CZECANCA panel (226 genes). 46/248 (18.5 %) carriers PVs established genes, primarily BRCA2 (N = 34), frequently BRCA1 7)...
Ovarian cancer is a disease with high mortality. Approximately 1,000 women are diagnosed ovarian in the Czech Republic annually. Women harboring mutation cancer-predisposing genes face an increased risk of tumor development. Mutations BRCA1, BRCA2, BRIP1, and Lynch syndrome (RAD51C, RAD51D, STK11) associated cancer, mutations ATM, CHEK2, NBN, PALB2, BARD1 appear to increase risk. Our aim was examine frequency Republic.We analyzed 1,057 individuals including patients 617 non-cancer controls...