Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers

• Published in: Human molecular genetics Vol. 7; no. 2; pp. 195 - 202
• Main Authors: TO HOA THAI, FENGHE DU, MILLER, D. S, TRASK, B. J, BAER, R, BOWCOCK, A. M, TSAN, J. T, YING JIN, PHUNG, A, SPILLMAN, M. A, MASSA, H. F, MULLER, C. Y, ASHFAQ, R, MATHIS, J. M
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.1998
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma, Clear Cell - genetics; Alleles; Biological and medical sciences; Breast Neoplasms - genetics; Carcinoma, Ductal, Breast - genetics; Carcinoma, Endometrioid - genetics; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Lobular - genetics; Carrier Proteins - genetics; Cystadenocarcinoma, Papillary - genetics; DNA Mutational Analysis; DNA, Neoplasm - genetics; Endometrial Neoplasms - genetics; Exons - genetics; Female; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Humans; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; Mixed Tumor, Mullerian - genetics; Molecular Sequence Data; Neoplasms, Multiple Primary - genetics; Neoplastic Syndromes, Hereditary - genetics; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Sarcoma - genetics; Tumor Cells, Cultured; Tumor Suppressor Proteins; Tumors; Ubiquitin-Protein Ligases; Uterine Neoplasms - genetics; Human; Sporadic; Gene organization; Hereditary; Female genital diseases; Mammary gland diseases; Ovarian diseases; Ovary; Binding protein; Domain structure; Uterus; Uterine diseases; Genetics; Tumor; Mammary gland; Mutation; Tumor suppressor gene; Polymorphism
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/7.2.195

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.