BRCA2 mutations in primary breast and ovarian cancers

• Published in: Nature genetics Vol. 13; no. 2; pp. 238 - 240
• Main Authors: Lancaster, Johnathan M, Wooster, Richard, Mangion, Jonathon, Phelan, Catherine M, Cochran, Charles, Gumbs, Curtis, Seal, Sheila, Barfoot, Rita, Collins, Nadine, Bignell, Graham, Patel, Sandeep, Hamoudi, Rifat, Larsson, Catharina, Wiseman, Roger W, Berchuck, Andrew, Iglehart, J. Dirk, Marks, Jeffrey R, Ashworth, Alan, Stratton, Michael R, Futreal, P. Andrew
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.06.1996
• Subjects: Aged; Base Sequence; Biological and medical sciences; BRCA2 Protein; Breast Neoplasms - genetics; DNA Primers; Female; Genetic Markers; Gynecology. Andrology. Obstetrics; Heterozygote; Humans; Lymphocytes - physiology; Mammary gland diseases; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Molecular Sequence Data; Mutation; Neoplasm Proteins - genetics; Ovarian Neoplasms - genetics; Retinoblastoma Protein - genetics; Sequence Deletion; Transcription Factors - genetics; Tumors; Human; Mammary gland diseases; Ovary; Sporadic; Somatic cell; Genetics; Heterozygosity loss; Tumor; Mammary gland; Mutation; Tumor suppressor gene
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0696-238

The second hereditary breast cancer gene, BRCA2, was recently isolated. Germline mutations of this gene predispose carriers to breast cancer, and, to a lesser extent, ovarian cancer. Loss of heterozygosity (LOH) at the BRCA2 locus has been observed in 30-40% of sporadic breast and ovarian tumours, implying that BRCA2 may act as a tumour suppressor gene in a proportion of sporadic cases. To define the role of BRCA2 in sporadic breast and ovarian cancer, we screened the entire gene for mutations using a combination of techniques in 70 primary breast carcinomas and in 55 primary epithelial ovarian carcinomas. Our analysis revealed alterations in 2/70 breast tumours and none of the ovarian carcinomas. One alteration found in the breast cancers was a 2-basepair (bp) deletion (4710delAG) which was subsequently shown to be a germline mutation, the other was a somatic missense mutation (Asp3095Glu) of unknown significance. Our results suggest that BRCA2 is a very infrequent target for somatic inactivation in breast and ovarian carcinomas, similar to the results obtained for BRCA1.