Isolation of Novel Prostate Cancer Tumor Suppressor Genes in African American and Caucasian Men thru Laser Microdissection and Representational Difference Analysis

摘要

We used RDA to identify homozygously deleted DNA clones within metastatic prostate cancer xenograft DNA, and found that all of the homozygously deleted clones mapped to a single region of chromosome 12p. We confirmed that the metastatic lesions from this patient also contained this homozygous deletion, and then analyzed this region in a series of 41 metastatic tumors from 19 patients, where we found that 50% of patients' tumors show loss. This 12p deletion occurs with similar frequency in caucasians and african-americans based on our small sample. We mapped this genomic region, and found that two previously identified potential candidate genes ETV(tel) and CDKN1B(p27) are located there. Analysis of these genes has revealed no sequence changes consistent with an important tumor suppressor role. Extensive analysis of p27 for possible mutational or methylation changes was negative. Major observations from our work include the finding of a homozygous deletion on chromosome 12p in metastatic prostate cancer, considered to be a major indicator that an important gene is nearby on chromosome 12p. Further analysis of this region revealed unexpected high degree of allelic loss in this region. Specific genes in the region were analyzed, and p27 appears to be the likely target, inactivated by loss of one copy. Further analysis was curtailed due to lack of funding.