Lenka Stolařová
A5061893016- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- Genomics and Rare Diseases
- DNA Repair Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Cutaneous Melanoma Detection and Management
- Microtubule and mitosis dynamics
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Gene expression and cancer classification
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
Czech Academy of Sciences, Institute of Molecular Genetics
2020-2024
Czech Academy of Sciences
2020-2023
Charles University
2018-2020
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...
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...
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....
Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of and other cancers. To assess spectrum variants, we analyzed 264 Czech patients indicated for testing due to early (at <25 years) or presence multiple primary melanoma/melanoma cancer their personal and/or family history. All were by panel next-generation sequencing targeting 217 four groups: high-to-moderate...
Polo-like kinases play essential roles in cell cycle control and mitosis. In contrast to other members of this kinase family, PLK3 has been reported be activated upon cellular stress including DNA damage, hypoxia osmotic stress. Here we knocked out human non-transformed RPE cells using CRISPR/Cas9-mediated gene editing. Surprisingly, find that loss does not impair stabilization HIF1α after hypoxia, phosphorylation the c-Jun dynamics damage response exposure ionizing radiation. Similarly,...
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.
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...
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...
<p>Detail description of the functional categorization analyzed CHEK2 missense variants.</p>
<p>Characteristics of 12 case-control datasets from the ENIGMA consortium partners.</p>
<p>Detail description of the functional categorization analyzed CHEK2 missense variants.</p>
<p>List of all analyzed CHEK2 variants with results KAP1/CHK2 kinase and localization assays the from recent previously published functional analyses VUS.</p>
<p>Characteristics of 12 case-control datasets from the ENIGMA consortium partners.</p>
<div>AbstractPurpose:<p>Germline pathogenic variants in <i>CHEK2</i> confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced screening. Besides variants, dozens of missense uncertain significance (VUS) have been identified, hampering the clinical utility germline genetic testing (GGT).</p>Experimental Design:<p>We collected 460 VUS identified by ENIGMA consortium 15 countries. Their functional characterization...
<p>Frequencies of all reported germline CHEK2 variant carriers and variants concordantly categorized by functional our kinase assays in breast cancer patients controls 12 analyzed population datasets.</p>
<p>List of all analyzed CHEK2 variants with results KAP1/CHK2 kinase and localization assays the from recent previously published functional analyses VUS.</p>