Prostate Cancer Aggressiveness Locus on Chromosome 7q32-q33 Identified by Linkage and Allelic Imbalance Studies

Neoplasia. Sep-Oct 2002;4(5):424-31. doi: 10.1038/sj.neo.7900254.

Abstract

The biologic aggressiveness of prostate tumors is an important indicator of prognosis. Chromosome 7q32-q33 was recently reported to show linkage to more aggressive prostate cancer, based on Gleason score, in a large sibling pair study. We report confirmation and narrowing of the linked region using finer-scale genotyping. We also report a high frequency of allelic imbalance (AI) defined within this locus in a series of 48 primary prostate tumors from men unselected for family history or disease status. The highest frequency of AI was observed with adjacent markers D7S2531 (52%) and D7S1804 (36%). These two markers delineated a common region of AI, with 24 tumors exhibiting interstitial AI involving one or both markers. The 1.1-Mb candidate region contains relatively few transcripts. Additionally, we observed positive associations between interstitial AI at D7S1804 and early age at diagnosis (P=.03) as well as a high combined Gleason score and tumor stage (P=.06). Interstitial AI at D7S2531 was associated with a positive family history of prostate cancer (P=.05). These data imply that we have localized a prostate cancer tumor aggressiveness loci to chromosome 7q32-q33 that is involved in familial and nonfamilial forms of prostate cancer.

MeSH terms

  • Aged
  • Allelic Imbalance / genetics*
  • Chromosomes, Human, Pair 7 / genetics*
  • DNA, Neoplasm / genetics
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neoplasm Staging
  • Prostatic Neoplasms / genetics*
  • Radiation Hybrid Mapping

Substances

  • DNA, Neoplasm