Nature Genetics
9, 439 - 443 (1995)
doi:10.1038/ng0495-439
Somatic mutations in the BRCA1 gene in sporadic ovarian tumoursSofia D. Merajver1, Trinh M. Pham1, Rosemarie F. Caduff2, Martha Chen1, Ellen L. Poy2, Kathleen A. Cooney1, Barbara L. Weber3, Francis S. Collins4, Carolyn Johnston5
& Thomas S. Frank2
1Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
2Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
3Departments of Genetics and Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
4National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA
5Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA Correspondence should be addressed to S.D.M. The BRCA1 gene on chromosome 17q21 is responsible for an autosomal dominant syndrome of increased susceptibility to breast and ovarian cancer but no somatic mutations in tumours have yet been described. To study the potential role of BRCA1 in sporadic carcinogenesis, we analysed the genomic DNA of tumour and normal fractions of 47 ovarian cancers for mutations in BRCA1 using the single−strand conformation polymorphism technique. We now describe somatic mutations in the DNA of four tumours which also had loss of heterozygosity (LOH) at a BRCA1 intragenic marker. Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers.
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