Prostate cancer aggressiveness locus on chromosome segment 19q12–q13.1 identified by linkage and allelic imbalance studies
✍ Scribed by Phillippa J. Neville; David V. Conti; Lisa M. Krumroy; William J. Catalona; Brian K. Suarez; John S. Witte; Graham Casey
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 120 KB
- Volume
- 36
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
Abstract
Whole‐genome scan studies recently identified a locus on chromosome segments 19q12–q13.11 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 (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI 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. © 2003 Wiley‐Liss, Inc.