Gene Discovery in Prostate Cancer: Functional Identification and Isolation of PAC-1, a Novel Tumor Suppressor Gene Within Chromosome 10p
Final rept. 1 Sep 1998-31 Aug 2001
M D ANDERSON CANCER CENTER HOUSTON TX
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The purpose and scope of this project was to utilize a functional approach for the physical mapping and identification of a novel tumor suppressor gene for prostate cancer within chromosome l0p. The major findings include the development of a technology for serial microcell fusion to transfer defined lop fragments into a mouse A9 fibrosarcoma cell line. Once characterized by FISH and microsatellite analyses, the l0p fragments were subsequently transferred into PC-3H to generate a panel of microcell hybrid clones containing overlapping deletions of chromosome l0p. In vivo and micro satellite analyses of these PC hybrids identified a small chromosome lop fragment an estimated 31 Mb in size inclusive of the centromere that when transferred into the PC-3H background, resulted in significant tumor suppression and limited a region of functional tumor suppressor activity to chromosome 10p12.31-q11. This region coincides with a region of LOH demonstrated in prostate cancer. These studies demonstrate the utility of this approach as a powerful tool to limit regions of functional tumor suppressor activity. Furthermore, these data used in conjunction with data generated by the Human Genome Project lent a focused approach to identify candidate tumor suppressor genes involved in prostate cancer.
- Anatomy and Physiology
- Medicine and Medical Research