Identification of BRCA1 and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning.
Abstract
After the identification of BRCA1, it became evident that some breast and prostate tumors show allelic loss on chromosome 17q12-21 very close to, but not including, the BRCAl locus. Therefore, we have analyzed two regions approximately 1Mb proximal and 1Mb distal to BRCAl, which show well defined loss of heterozygosity in sporadic breast tumors and sporadic prostate tumors respectively, to identify additional candidate tumor suppressor genes. Transcripts from these regions were identified using genomic reagents from our 4.5-Mb physical contig that contains the BRCA1 gene. Two novel members of the dlg2 and dlg3 disc-large family of genes, and a gene encoding an ADP-ribosylation factor (ARF4L) were identified in the distal region. In the proximal region we identified the plakoglobin gene, which previously had been thought to be located on chromosome 7. Plakoglobin, dlg2 and dlg3 are believed to be molecular components of cell-cell junctions, whereas ARF4L is believed to be involved in protein secretion and signal transduction. Several prominent tumor suppressor genes including the adenomatous polyposis coli gene (APC) and the Drosophila discs-large gene (Dlg) are components of cell-cell junctions, making three of the novel genes we identified and/or placed in the genomic region surrounding BRCA1 particularly interesting candidates for further investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 26, 1995
- Accession Number
- ADA299498
Entities
People
- Raymond L. White
Organizations
- University of Utah