Mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers, and therefore sequence analysis of both genes is routinely conducted in patients with early-onset breast cancer.
The relevance of many BRCA2 variants of uncertain significance (VUS) to breast cancer has not been determined due to limited genetic information from families carrying these alterations.
Approximately 120 distinct missense variants have been identified in the BRCA1 BRCT through breast cancer screening, and several of these have been linked to an increased cancer risk.
In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function.
The entire coding regions of the two breast cancer susceptibility genes BRCA1 and BRCA2 from breast cancer patients from 40 Cypriot families with multiple cases of breast and ovarian cancer were sequenced.
Some studies have shown that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer.
These predictions revealed that BRCA2 T2722R (8393C-->G), which segregates with affected individuals in a family with breast cancer, disrupts three potential ESE sites.
Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case.
We analysed by direct sequencing the BRCA2 gene in 29 breast cancer patients derived from 29 families with an aggregation of at least one female breast cancer diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years.
Breast cancer is a rare disease in men.Germ-line mutations in BRCA2 and androgen receptor (AR) genes are thought to be responsible for a proportion of male breast cancer cases.