Identification of BRCA1 and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning.
Annual rept. 1 Jul 94-30 Jun 95,
UTAH UNIV SALT LAKE CITY
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After the identification of BRCA 1, it became evident that some breast and prostate tumors show allelic loss on chromosome l7ql2-2l very close to, but not including, the BRCAl locus. These observations strongly suggests the presence of important tumor suppressor genes at these two locations. 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 BRCAi 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 DIg are components of cell-cell junctions, making three of the novel genes we identified andor placed in the genomic region surrounding BRCAl particularly interesting candidates for further investigation.
- Anatomy and Physiology
- Genetic Engineering and Molecular Biology