PURPOSE Lung cancer cells frequently exhibit marked chromosome instability. We postulated that alterations of the double-strand break repair genes (BRCA1, BRCA2, and XRCC5) might be involved in lung cancer. PATIENTS AND METHODS We examined the loss of protein and mRNA expression and the 5'CpG hypermethylation and allelic imbalance of the BRCA1, BRCA2, and XRCC5 genes in 98 non-small cell lung...

PURPOSE BRCA1/BRCA2 germline mutations appear to enhance the platinum-sensitivity, but little is known about the prognostic relevance of polymorphisms in BRCA1/BRCA2 in epithelial ovarian cancer (EOC). This study evaluated whether common variants of BRCA1/BRCA2 are associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced stage sporadic EOC. EXPERIMEN...

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate...

PURPOSE Most familial breast cancers are not associated with BRCA1 or BRCA2 germ-line mutations. Therefore, it is of major importance to define the morphological, immunohistochemical, and molecular features of this group of tumors to improve genetic testing and also gain further insight into the biological characteristics of tumors. EXPERIMENTAL DESIGN We evaluated the morphological character...

Recently, BRCA1 germline mutations were found in a high proportion (14-34%) of patients with triple-negative breast cancer (TNBC). BRCA2 was either not analyzed or showed much lower mutation frequencies. Therefore, we screened a group of TNBC patients (n = 30) of white European descent for mutations in BRCA2 as well as in BRCA1. Cases were unselected for age of disease-onset (median age at brea...

Mutations in BRCA1 and BRCA2 account for the majority of familial breast cancers. Cells with mutated BRCA1 or BRCA2 are hypersensitive to ionizing radiation (IR) and exhibit defective DNA repair. Both BRCA1 and BRCA2 have been reported to bind Rad51, a protein essential for homologous recombination and the recombinational repair of DNA double-strand breaks. In normal cells, a redistribution of ...

PURPOSE To determine prospectively overall and age-specific estimates of contralateral breast cancer (CBC) risk for young patients with breast cancer with or without BRCA1/2 mutations. PATIENTS AND METHODS A cohort of 6,294 patients with invasive breast cancer diagnosed under 50 years of age and treated between 1970 and 2003 in 10 Dutch centers was tested for the most prevalent BRCA1/2 mutati...

9 Five to ten per cent of all breast carcinomas are of hereditary origin. Many of them have been associated to 10 mutations in the BRCA1 and BRCA2 susceptibility genes. No ‘‘BRCA3’’ gene has been found to account for 11 the non-BRCA1/BRCA2 breast cancer (BRCAx) families, and BRCAx tumors are increasingly believed to 12 originate from multiple distinct genetic events. Phenotype studies have ques...

The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations....

Although ovarian carcinomas with mutated BRCA1 or BRCA2 are sensitive to platinum compounds, such carcinomas eventually develop platinum resistance. Previously, we showed that acquired resistance to cisplatin in BRCA2-mutated tumors can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. Here, we show that secondary mutations of BRCA1 also occu...