A5042164221- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Nutrition, Genetics, and Disease
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Genetics, Bioinformatics, and Biomedical Research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- Ovarian cancer diagnosis and treatment
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Colorectal Cancer Treatments and Studies
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- PARP inhibition in cancer therapy
- Biochemical and Molecular Research
- Molecular Biology Techniques and Applications
- Male Breast Health Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics and Neurodevelopmental Disorders
- Regulation of Appetite and Obesity
Charles University
2016-2025
General University Hospital in Prague
2016-2025
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2019
Research Institute of Inorganic Chemistry
2019
Pfizer (United Kingdom)
2018
AstraZeneca (Brazil)
2018
Maastricht University
2018
Bristol-Myers Squibb (Germany)
2018
Clovis Oncology (United Kingdom)
2018
Myriad (Germany)
2018
PURPOSE To estimate age-specific relative and absolute cancer risks of breast to ovarian, pancreatic, male breast, prostate, colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these have not been extensively characterized. METHODS We analyzed data from 524 families PVs 21 countries. Complex segregation analysis was used (RRs; country-specific population incidences) cancers. The models allowed for residual familial aggregation ovarian were adjusted the...
The DNA damage response (DDR) pathway and its core component tumor suppressor p53 block cell cycle progression after genotoxic stress represent an intrinsic barrier preventing cancer development. serine/threonine phosphatase PPM1D/Wip1 inactivates promotes termination of the DDR pathway. Wip1 has been suggested to act as oncogene in a subset tumors that retain wild-type p53. In this paper, we have identified novel gain-of-function mutations exon 6 PPM1D result expression C-terminally...
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...
// Sona Pechackova 1, * , Kamila Burdova Jan Benada 1 Petra Kleiblova 2 Gabriela Jenikova Libor Macurek Department of Cancer Cell Biology, Institute Molecular Genetics the ASCR, CZ-14220 Prague, Czech Republic Biochemistry and Experimental Oncology, Charles University in CZ-12853 These authors have contributed equally to this work Correspondence to: Macurek, e-mail: libor.macurek@img.cas.cz Keywords: WIP1 inhibitor, p53, checkpoint, nutlin-3, breast cancer Received: October 31, 2015...
Atypical polypoid adenomyoma (APA) is an uncommon uterine lesion that commonly recurs after local excision and occasionally associated with or precedes the development of atypical hyperplasia endometrioid adenocarcinoma. Despite fact about 230 cases have been reported in literature, only 2 studies 6 7 investigated molecular aspects; as such, alterations occur APA remain largely unknown. We undertook a comprehensive immunohistochemical analysis 21 17 patients (including 4 recurrent/persistent...
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....
Abstract RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, has been implicated in homologous recombination; however, function incompletely understood. Here, we show recruited to lesions monoubiquitination of histone H2A at K15 counteracts accumulation 53BP1. Super-resolution microscopy revealed localizes the proximity double strand breaks limits distribution 53BP1 peripheral...
Germline DNA testing using the next-gene-ration sequencing (NGS) technology has become analytical standard for diagnostics of hereditary diseases, including cancer. Its increasing use places high demands on correct sample identification, independent confirmation prioritized variants, and their functional clinical interpretation. To streamline these processes, we introduced parallel RNA capture-based NGS identical capture panel CZECANCA, which is routinely used analysis cancer predisposition....
Introduction Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background RCC native kidneys has been determined, implicating its clinical importance. Materials and methods This retrospective single-center pilot study aimed to identify a potential genetic predisposition transplanted outcome KTR who underwent single transplantation between January 2000 December 2020 manifested kidney. Next-generation sequencing (NGS) based...
Alterations in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism contribute to development serious FPs-related toxicity. We performed mutation analysis DPYD based on cDNA sequencing 76 predominantly colorectal cancer patients treated by FPs with early high (grade 3-4) hematological and/or gastrointestinal Six previously described [85T>C (C29R), 496A>G (M166V), 775A>G (K259E), 1601G>A (S534N), 1627A>G (I543V), IVS14+1G>A, 2194G>A...
Summary Objective To study the influence of chronic malnutrition in patients with anorexia nervosa on endocrine function adipose tissue both circulating and subcutaneous fat mRNA expression level. Patients design A total 12 18 normal weight age‐matched women underwent anthropometric examination, single blood drawing biopsy. Measurements Serum concentrations high‐sensitive CRP (hsCRP), leptin, soluble leptin receptor, adiponectin, resistin, interleukin‐6 insulin were measured by Luminex,...
Several reports indicate that inherited mutations in the PALB2 gene predispose to breast cancer. However, there is little agreement about clinical relevance and usefulness of mutation screening this gene. We analyzed prevalence spectrum germline estimate their contribution hereditary and/or ovarian cancer Czech Republic.The entire coding region was sequenced 409 breast/ovarian patients negative for BRCA1 BRCA2 mutations. Testing large genomic rearrangements (LGR) performed by multiplex...
The checkpoint kinase 2 gene (CHEK2) codes for the CHK2 protein, an important mediator of DNA damage response pathway. CHEK2 has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL) remains unclear. We performed mutation analysis entire coding sequence 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Identified hereditary variants were genotyped 445...
Hereditary breast cancer comprises a minor but clinically meaningful ( BC ) subgroup. Mutations in the major ‐susceptibility genes are important prognostic and predictive markers; however, their carriers represent only 25% of high‐risk patients. To further characterize variants influencing risk, we performed SOLiD sequencing 581 325 patients (negatively tested previous BRCA1 / BRCA2 PALB2 analyses). In 105 (32%) patients, identified confirmed 127 truncating (89 unique; nonsense, frameshift...
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...
Abstract The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis 123 early-onset OC-patients compared to histology/stage-matched unselected OC-patients, population-matched controls. Only 6/123(4.9%) carried pathogenic variant (GPV) high-penetrance OC-predisposition genes. Nevertheless,...
The Guidelines for Clinical Practice carriers of pathogenic variants in clinically relevant cancer predisposition genes define the steps primary and secondary prevention that should be provided to these individuals at high risk developing hereditary Czech Republic. drafting guidelines was organized by Oncogenetics Working Group Society Medical Genetics Genomics J. E. Purkyně (SLG ČLS JEP) cooperation with representatives oncology oncogynecology. are based on current recommendations National...