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- Title
Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.
- Authors
Thai, T H; Du, F; Tsan, J T; Jin, Y; Phung, A; Spillman, M A; Massa, H F; Muller, C Y; Ashfaq, R; Mathis, J M; Miller, D S; Trask, B J; Baer, R; Bowcock, A M
- Abstract
Germline alterations of BRCA1 result in susceptibility to breast and ovarian cancer. The protein encoded by BRCA1 interacts in vivo with the BRCA1-associated RING domain (BARD1) protein. Accordingly, BARD1 is likely to be a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. We have now determined the genomic structure of BARD1 and performed a mutational analysis of 58 ovarian tumors, 50 breast tumors and 60 uterine tumors. Seven polymorphisms were detected within the 2.34 kb coding sequence of BARD1 . Somatically acquired missense mutations were observed in one breast carcinoma and one endometrial tumor; in at least one of these cases, tumor formation was accompanied by loss of the wild-type BARD1 allele, following the paradigm for known tumor suppressor genes. In addition, a germline alteration of BARD1 was identified in a clear cell ovarian tumor (Gln564His); again, loss of the wild-type BARD1 allele was observed in the malignant cells of this patient. The Gln564His patient was also diagnosed with two other primary cancers: a synchronous lobular breast carcinoma and a stage IA clear cell endometrioid cancer confined to an endometrial polyp 6 years earlier. These findings suggest an occasional role for BARD1 mutations in the development of sporadic and hereditary tumors.
- Publication
Human molecular genetics, 1998, Vol 7, Issue 2, p195
- ISSN
0964-6906
- Publication type
Journal Article
- DOI
10.1093/hmg/7.2.195