Increased level of exon 12 alternatively spliced BRCA2 transcripts in tumor breast tissue compared with normal tissue.
The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript encoding a 3418-amino acid protein, which is involved in the response to DNA damage. To obtain a better molecular characterization of BRCA2 expression in breast tissue, we analyzed full-length BRCA2 mRNA by means of reverse transcriptase-PCR with a panel of primer pairs encompassing the entire cDNA sequence. We report the identification of an exon 12 alternatively spliced BRCA2 transcript (delta12-BRCA2) in normal human breast tissue, in a wide variety of other normal human tissues, and in several mouse tissues. The deletion observed in this transcript (96 bp) preserves the open reading frame, and translation of the transcript would result in a BRCA2 isoform lacking 32 amino acids between codons 2280 and 2311. The analysis of matched normal and primary tumor breast tissues from 12 patients showed that the expression level of the delta12-BRCA2 transcript was higher in 4 of 12 (33%) tumor tissues compared with their normal breast tissues. Overproduction of the delta12-BRCA2 variant was associated with steroid receptor-negative tumors (P = 0.0005). These data suggest that the mechanisms generating the BRCA2 mRNA variant exist in normal breast tissue and may be dysregulated in steroid receptor-negative breast tumor tissues.
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Laboratoire d'Oncogénétique, Centre René Huguenin, St-Cloud, France.
Lidereau
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D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D005091:Exons; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors