Germline mutations in BRCA1 and BRCA2 predispose to common human malignancies, most notably tumors of the breast and ovaries. The proteins encoded by these genes have been implicated in a plethora of biochemical interactions and biological functions, confounding attempts to coherently explain how their inactivation promotes carcinogenesis. Here, I argue that tumor suppression by BRCA1 and BRCA2...

The development of poly (adenosine diphosphate [ADP]) ribose polymerase (PARP) inhibitors (PARPi) has progressed greatly over the last few years and has shown encouraging results in the BRCA1/2 mutation-related cancers. This article attempts to summarize the rationale and theory behind PARPi, the clinical trials already reported, as well as ongoing studies designed to determine the role of PARP...

Anticipating that genetic tests designed to determine an individuals predisposition to disease would eventually become commercially available, and recognizing that the results of many of these tests may have mortality implications, in 1994 Lincoln National Reinsurance Companies began developing a methodology that would allow the mortality risk associated with a number of different genetic mutat...

1512 Background: The frequency of a BRCA mutation among women with ductal carcinoma in situ (DCIS) has not been well described. Consequently, patients with DCIS were not historically considered ideal candidates for genetic testing even in the presence of a family history of breast and ovarian cancer. Therefore, we examined the prevalence of BRCA1/2 mutations in women diagnosed with DCIS. METH...

Germline mutations in BRCA1/2 genes are responsible for a large proportion of hereditary breast and/or ovarian cancers. Many highly penetrant predisposition alleles have been identified and include frameshift or nonsense mutations that lead to the translation of a truncated protein. Other alleles contain missense mutations, which result in amino acid substitution and intronic variants with spli...

More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65-85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syn...

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC highlight the discordance between strategies across two centres. Patients were counselled consented by MDT member. The uptake multi-gene was 97.7%. Counselling clinical-...

OBJECTIVES To compare clinical-pathological characteristics and outcome between sporadic ovarian cancer and ovarian cancer in patents with hereditary breast and ovarian cancer syndrome (HBOC). METHODS Twenty-four patients with ovarian cancer treated between 2000 and 2009 who tested positive for BRCA1/2 mutation (BRCA+) and a control group of 64 age-matched patients with no family history of b...

PURPOSE The importance of the BRCA gene products in maintaining genomic stability led us to hypothesize that BRCA-associated and sporadic ovarian cancers would have distinctive genetic profiles despite similarities in histologic appearance. EXPERIMENTAL DESIGN A whole-genome copy number analysis of fresh, frozen, papillary serous ovarian cancer DNA was done using the Affymetrix 50K Xba Mappin...