The recent completion of the draft human genome sequence (1) presents countless opportunities to investigate genome function and the importance of alterations in the genetic code in both health and disease. Among the most rapidly adopted of the emerging genomic technologies, microarray hybridization permits the parallel determination of the expression of tens of thousands of genes in tissue sam...

We present a comprehensive analysis of 1,506 German families for large genomic rearrangements (LGRs) in the BRCA1 gene and of 450 families in the BRCA2 gene by the multiplex ligation-dependent probe amplification (MLPA) technique. A total of 32 pathogenic rearrangements in the BRCA1 gene were found, accounting for 1.6% of all mutations, but for 9.6% of all BRCA1 mutations identified in a total ...

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 functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases). 72 cell lines from affected women in high-risk breast ovaria...

H omologous recombination (HR) is a key pathway to repair complex DNA damage, such as DNA gaps, doublestrand breaks, and interstrand cross-links (1) (Fig. 1). Moreover, HR supports the recovery of stalled or broken replication forks and ensures faithful chromosome segregation during meiosis. The RAD52 gene in the budding yeast Saccharomyces cerevisiae encodes the lynchpin of HR in this organism...

Breast cancer is a rare disease in men, affecting less than 0.1% of the male population. Two heritable gene defects have been associated with a predisposition to male breast cancer development, i.e., germ-line muta tions in the breast cancer susceptibility gene BRCA2 and the androgen receptor (AR) gene. In this study, the entire coding regions OÕBRCA2and AR were screened for mutations in 34 co...

The products of the BRCA breast cancer susceptibility genes have been implicated in cell cycle control and DNA repair. It has been suggested that mutations in the p53 gene are a necessary step in tumorigenesis in BRCA tumors. We tested samples from 402 breast cancer patients for germ-line BRCA2 and p53 mutations in tumors. p53 mutations are more frequent in BRCA2 mutation carriers than they are...

BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334d...

PURPOSE The Breast Cancer Linkage Consortium and other family-based ascertainments have suggested that male carriers of BRCA mutations are at increased risk of prostate cancer. Several series looking at the frequency of BRCA mutations in unselected patients with prostate cancer have not confirmed this finding. To clarify this issue, we conducted a large case-control study. EXPERIMENTAL DESIGN...

Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complementation groups exist (FA-A to G), and the genes for all of these except FA-B ...