Prostate Cancer Aggressiveness Locus on Chromosome Segment 19q12-q13.1 Identified by Linkage and Allelic Imbalance Studies

Genes Chromosomes Cancer. 2003 Apr;36(4):332-9. doi: 10.1002/gcc.10165.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Allelic Imbalance / genetics*
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 19 / genetics*
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics*
  • Humans
  • Male
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Paraffin Embedding
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery

Substances

  • Genetic Markers