Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds.
BRCA1, a breast-ovarian cancer susceptibility gene which has been localized to 17q21, appears to be a tumor suppressor gene based on evidence from loss of heterozygosity (LOH) studies. We analyzed 14 ovarian and breast tumors from BRCA1 carriers and 1 sporadic breast tumor from 3 kindreds for 17q21 LOH. Thirteen of the 14 tumors from gene carriers exhibited LOH of the wild-type allele. Tumors from one gene carrier and the sporadic breast case did not exhibit any LOH in the region. There was loss of the wild-type allele from both maternally and paternally derived chromosomes, therefore excluding the possibility of genomic imprinting and providing further evidence that BRCA1 is a tumor suppressor. Three tumors showed interstitial LOH in the region, and thus established the utility of familial tumors in refining a region surrounding a tumor suppressor gene in a manner analogous to using genetic recombinants.
Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City 84132.
S L
SL
Neuhausen
C J
CJ
Marshall
D000328:Adult; D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D005260:Female; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors