Barbora Šťastná
A5026777142- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- RNA Research and Splicing
- Male Breast Health Studies
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Genomic variations and chromosomal abnormalities
- Immune Cell Function and Interaction
- Viral-associated cancers and disorders
- Ovarian cancer diagnosis and treatment
- Genomics and Chromatin Dynamics
- Genetic Associations and Epidemiology
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
Charles University
2023-2024
General University Hospital in Prague
2023-2024
Czech Academy of Sciences, Institute of Molecular Genetics
2024
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....
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 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.
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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 whole exome sequencing together with human leukocyte antigen(HLA) typing, polygenic risk score(PRS) assessment and survival analysis 123 early-onset patients compared to histology/stage-matched unselected patients, population-matched controls. Only 6/123(4.9%) carried pathogenic...
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)...
<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>
<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>Kinase KAP1 and CHK2 assays (<b>A</b>). The bar graphs show results of kinase for 430 <i>CHEK2</i> missense variants. In both assays, variants with normalized relative activity (mean WT-activity = 1) exceeding that the weakest signal WT replicas (not shown) were categorized functionally WT-like, intensity lower than strongest any kinase-dead/empty EGFP vector controls (in-frame exon 7 deletion–p.D265_H282del; not as impaired. Variants activities between these...
<p>Kinase KAP1 and CHK2 assays (<b>A</b>). The bar graphs show results of kinase for 430 <i>CHEK2</i> missense variants. In both assays, variants with normalized relative activity (mean WT-activity = 1) exceeding that the weakest signal WT replicas (not shown) were categorized functionally WT-like, intensity lower than strongest any kinase-dead/empty EGFP vector controls (in-frame exon 7 deletion–p.D265_H282del; not as impaired. Variants activities between these...
<p>Presence of analyzed <i>CHEK2</i> missense variants categorized according to the functional assays in patients with breast cancer (BC pts; red numbers) and matched controls (dark green numbers). The association risk (odds ratio; OR) were calculated for prevalent having ≥10 carriers among or controls, respectively. Colors numbers last column highlight significant moderate-or-higher (red; OR > 2), low (OR < protective (green) without impact on (black). Gray rows...
<p>Presence of analyzed <i>CHEK2</i> missense variants categorized according to the functional assays in patients with breast cancer (BC pts; red numbers) and matched controls (dark green numbers). The association risk (odds ratio; OR) were calculated for prevalent having ≥10 carriers among or controls, respectively. Colors numbers last column highlight significant moderate-or-higher (red; OR > 2), low (OR < protective (green) without impact on (black). Gray rows...