Prostate cancer aggressiveness locus on chromosome segment 19q12-q13.1 identified by linkage and allelic imbalance studies

Whole-genome scan studies recently identified a Iocus locus on chromosome segments 19q I 9q 12-ql3.11 q 13.1 1 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer-scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (Al) studies across this region in primary prostate tumors from 52 patients unselected for family history of disease status. A high level of Al was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of Al of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial Al involving one or both markers. In addition, we noted a positive association between Al at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12-q13.11 that may play a role in both familial and non-familial forms of prostate cancer.