A MOLECULAR CYTOGENETIC ANALYSIS OF 7Q31 IN PROSTATE-CANCER

Gains of chromosome 7 and alterations of the 7q-arm have been frequent ly observed in multiple cancers using various cytogenetic and molecula r 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 hybridizati on (FISH) with DNA probes for the chromosome 7 centromere and for 5 lo ci mapped to 7q31 (D7S523, D7S486, D7S522, D7S480, and D7S490) and 1 l ocus at 7q11.23 (ELN), Six tumors had no apparent anomaly for any chro mosome 7 probe, Nine tumors showed apparent simple gain of a whole chr omosome 7, whereas one tumor had apparent simple loss of a whole chrom osome 7. Four tumors had gain of the chromosome 7 centromere and addit ional overrepresentation of the 7q-arm, One tumor had overrepresentati on 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 chromo some 7 centromere and loss of the 7q31 region. Gain of 7q31 was strong ly correlated with tumor Gleason score, Multiplex PCR studies of these specimens supported these FISH observations, Mutation screening and D NA 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 aph idicolin-induced, chromosome 7 only, somatic cell hybrid demonstrated that the DNA probe for D7S522 spans the common fragile site FRA7G at 7 q31, Our data indicate that the 7q-arm, particularly the 7q31 region, is genetically unstable in prostate cancer, and some of the gene dosag e differences observed may be due to fragility at FRA7G.