A molecular cytogenetic analysis of 7q31 in prostate cancer

Cancer Res. 1998 Feb 15;58(4):759-66.

Abstract

Gains of chromosome 7 and alterations of the 7q-arm have been frequently observed in multiple cancers using various cytogenetic and molecular genetic techniques. Using PCR analysis of microsatellite markers, we have previously reported that allelic imbalance of 7q31 is common in prostate cancer and is associated with higher tumor grade and advanced pathological stage. In an effort to better understand the chromosome 7 alterations in prostate cancer, we undertook a molecular cytogenetic study of 25 prostate specimens using fluorescence in situ hybridization (FISH) with DNA probes for the chromosome 7 centromere and for 5 loci mapped to 7q31 (D7S523, D7S486, D7S522, D7S480, and D7S490) and 1 locus at 7q11.23 (ELN). Six tumors had no apparent anomaly for any chromosome 7 probe. Nine tumors showed apparent simple gain of a whole chromosome 7, whereas one tumor had apparent simple loss of a whole chromosome 7. Four tumors had gain of the chromosome 7 centromere and additional overrepresentation of the 7q-arm. One tumor had overrepresentation of 7q31 without any apparent anomaly of the chromosome 7 centromere, and one tumor had apparent loss of the chromosome 7 centromere with no apparent anomaly of the 7q-arm. Three tumors had gain of the chromosome 7 centromere and loss of the 7q31 region. Gain of 7q31 was strongly correlated with tumor Gleason score. Multiplex PCR studies of these specimens supported these FISH observations. Mutation screening and DNA sequencing of the MET gene, which is mapped to 7q31, revealed only the presence of simple sequence polymorphisms but no apparent acquired disease-associated mutations. FISH analysis of metaphases from an aphidicolin-induced, chromosome 7 only, somatic cell hybrid demonstrated that the DNA probe for D7S522 spans the common fragile site FRA7G at 7q31. Our data indicate that the 7q-arm, particularly the 7q31 region, is genetically unstable in prostate cancer, and some of the gene dosage differences observed may be due to fragility at FRA7G.

Publication types

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

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Breakage
  • Chromosome Deletion
  • Chromosome Fragile Sites
  • Chromosome Fragility*
  • Chromosomes, Human, Pair 7*
  • DNA Mutational Analysis
  • Gene Dosage
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Monosomy
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / genetics*
  • Proto-Oncogene Proteins / genetics
  • Trisomy

Substances

  • Proto-Oncogene Proteins