A region on chromosome 1, 1q24-q31, is believed to harbor a prostate cancer susceptibility gene, known as HPC1. Our group originally identified this locus through genetic linkage analysis using a large set of high risk prostate cancer families. As of last year, this group had completed the construction of a high resolution physical map that was used for genetic marker and candidate gene mapping. This physical map, consisting primarily of bacterial artificial chromosomes, has served as the template for sequencing of the 1q25 region for the human genome project. Over the past year, we have mapped a total of 75 potential candidate genes in the HPC1 region. A number of these genes, which were originally partial transcripts have been extended into full length transcripts and have been characterized for patterns of tissue expression by Northern analysis. We have also used computational biology to identify novel predicted genes from draft human genome sequence. We have screened approximately 60 of these candidate genes for germline mutations in prostate cancer patient DNA samples. We have recently identified and published mutations in the RNASEL gene in several families with HPC1 linked hereditary prostate cancer. Several manuscripts have been recently reported by others showing some level of association of RNASEL variants with prostate cancer risk. To date four manuscripts have been published from this work.
