A5032232631- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Nutrition, Genetics, and Disease
- Genomics and Rare Diseases
- Ovarian cancer diagnosis and treatment
- Biological Research and Disease Studies
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Genomic variations and chromosomal abnormalities
Taibah University
2020-2023
McGill University
2017-2023
McGill University Health Centre
2020-2023
Not all familial ovarian cancer (OC) cases are explained by pathogenic germline variants in known risk genes. A candidate gene approach involving DNA repair pathway genes was applied to identify rare recurring OC not associated with from a population exhibiting genetic drift. Whole exome sequencing (WES) data of 15 13 families tested negative for were investigated 468 Filtering and prioritization criteria WES select top candidates further analyses. Candidates genotyped ancestry defined study...
Abstract Background Familial ovarian cancer (OC) cases not harbouring pathogenic variants in either of the BRCA1 and BRCA2 OC-predisposing genes, which function homologous recombination (HR) DNA, could involve other DNA repair pathway genes. Methods Whole exome sequencing was used to identify rare HR genes a variant negative OC family French Canadian (FC) ancestry, population exhibiting genetic drift. cancer-free individuals from FC non-FC populations were investigated for carrier frequency...
FANCI was recently identified as a new candidate ovarian cancer (OC)-predisposing gene from the genetic analysis of carriers c.1813C>T; p.L605F in OC families. Here, we aimed to investigate molecular characteristics FANCI, they have not been described context cancer. We first investigated germline landscape two sisters with discovery family (F1528) re-affirm plausibility this candidate. As did find other conclusive candidates, then performed approach identify variants genes involved protein...
Background: Detecting pathogenic intronic variants resulting in aberrant splicing remains a challenge routine genetic testing. We describe germline whole-exome sequencing (WES) analyses and apply silico predictive tools of familial ovarian cancer (OC) cases reported clinically negative for BRCA1 BRCA2 variants. Methods: WES data from 27 OC 53 sporadic early-onset were analyzed or BRCA2. carriers 10 other predisposing genes. Loss heterozygosity analysis was performed on tumor DNA variant...
To identify candidate variants in RAD51C and RAD51D ovarian cancer (OC) predisposing genes by investigating French Canadians (FC) exhibiting unique genetic architecture. Candidates were identified whole exome sequencing analysis of 17 OC families 53 early-onset cases. Carrier frequencies determined the 100 or HBOC families, 438 sporadic cases 1025 controls. Variants unknown function assayed for their biological impact and/or cellular sensitivity to olaparib. c.414G>C;p.Leu138Phe...
Abstract Some familial ovarian cancer (OC) could be due to rare risk alleles in genes that each account for a relatively small proportion of cases not BRCA1 and BRCA2 , major the homologous recombination (HR) DNA repair pathway. We report new candidate OC allele, FANCI c.1813C>T Fanconi anemia (FA) gene plays role upstream HR This variant was identified by whole exome sequencing mutation-negative French Canadian (FC) family from population exhibiting founder effects. In FCs, allele...
ABSTRACT Five rare variants in BRIP1/FANCJ , initially reported ovarian (OC) or breast (BC) cancer cases by the adult hereditary clinics, were investigated for their candidacy as clinically relevant variants. These genetically a population exhibiting genetic drift and molecularly assayed biological impact. Using silico tools, population-based databases other resources, three of five BRIP1 likely to be damaging: c.797C>T; p.Thr266Met, c.2087C>T; p.Pro696Leu c.2990_2993delCAAA;...
Abstract Recurrent mutations in BRCA1 and BRCA2, which are genes that play a major role the homologous recombination (HR) DNA repair pathway, account for significant proportion of hereditary breast cancer (HBC) or breast-ovarian (HBOC) families French Canadian (FC) descent due to common founders. This has facilitated genetic testing establishing germline mutation carrier status clinics Quebec offering surveillance prevention options women at risk other cancers. Recent evidence suggests rare...
Abstract The potentially pathogenic variant (PPV), FANCI c.1813C>T; p.L605F, in a new candidate ovarian cancer (OC) predisposing gene was discovered by whole exome sequencing (WES) of familial OC cases from the founder French Canadian (FC) population for discovering genes. Modeling this cellulo suggested encodes an unstable protein. is essential member upstream homologous recombination DNA repair pathway and intersects BRCA1 BRCA2 function, proteins encoded genes involved hereditary...