We provide genetic evidence supporting the identity of the candidate gene for BRCA1 through the characterization of germline mutations in 63 breast cancer patients and 10 ovarian cancer patients in ten families with cancer linked to chromosome 17q21.
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.
In this report we present the results of mutational analysis of the BRCA2 coding sequences in 105 high-risk individuals affected with breast cancer and/or ovarian cancer and previously found to be negative for mutations of the BRCA1 coding sequence in our laboratory.
These predictions revealed that BRCA2 T2722R (8393C-->G), which segregates with affected individuals in a family with breast cancer, disrupts three potential ESE sites.
Eighteen mutations in BRCA1 were detected in 11/28 breast/ovarian cancer families and 7/33 breast cancer families and none in the families with only two cases.
Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.
Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.
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.
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.