CHARACTERIZATION OF FUNCTIONAL MESSENGER-RNA SPLICE VARIANTS OF BRCA1EXPRESSED IN NONMALIGNANT AND TUMOR-DERIVED BREAST CELLS

BRCA1 has been identified as a tumor suppressor gene that is mutated i n many cases of inherited breast and ovarian cancer. Recent data sugge st that multiple splice forms of BRCA1 exist, but the structure and fu nction of these alternative transcripts hare not been elucidated. By s equence analysis of reverse transcription-PCR products, we have determ ined that a major splice form of BRCA1 expressed in malignant and nonm alignant breast epithelial cells contains an in-frame deletion of 3309 nucleotides from exon 11. A second alternative splice event results i n the in-frame deletion of the 123 nucleotides that make up exons 3 an d 10. These splice variants are found on polysomes and are therefore p redicted to encode 80-85-kDa BRCA1-derived proteins lacking approximat ely 60% of the internal amino acids that constitute full-length BRCA1.