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Identification of BRCA1 and 2 Other Tumor Suppressor Genes on Chromosome 17 Through Positional Cloning

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Annual rept. 1 Jul 1995-30 Jun 1996

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During the past year we have made good progress on several aspects of the research outlined in our original proposal. In particular, we have identified the human homologue of the mouse FKBP65 gene and a novel gene with strong protein homology to an uncharacterized gene in C. legans in the region of LOH surrounding plakoglobin, a region which is lost in human breast tumors. We have also begun to establish a physical map in the telomeric region of the short arm of chromosome 17, as art of an approach to cloning the tumor suppressor genes thought to be present there. In the process, by comparing available LOH mapping information with our genetic maps we have identified a preliminary 15-cM target region for the putative tumor suppressor genes. In our other focus of investigation, we are characterizing the biological effects of inhibiting the two DLG genes we have identified as located 1Mb telomeric of BRCA1. We have also tested 9 paired samples of breast tumors and corresponding normal tissues for LOH in the region containing the DLG2 and DLG3 loci. As 3 of the tumors in these sets exhibited LOH, we are determining whether either the DLG2 or DLG3 gene is the target by means of sequencing experiments based on templates prepared from RNA isolated from all the tumors showing LOH. In one sample tested for LOH, micro-satellite instability was observed.

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  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

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