FREQUENT LOSS OF HETEROZYGOSITY AT 7Q31.1 IN PRIMARY PROSTATE-CANCER IS ASSOCIATED WITH TUMOR AGGRESSIVENESS AND PROGRESSION

Cytogenetic analyses have demonstrated that chromosome region 7q22-32 is commonly altered in prostate adenocarcinomas. Tn addition, in recen t fluorescence in situ hybridization studies, we have observed that an eusomy of chromosome 7 is frequent in prostate cancer and is associate d with higher tumor grade, advanced pathological stage, and early pros tate cancer death. These findings suggest that genetic alterations of chromosome 7 play a significant role in the development of prostate ca ncer. To better define the chromosome 7 alterations, PCR analysis of 2 1 microsatellite loci was performed on 54 paired prostate cancer and c ontrol DNAs. Overall, chromosome 7 allelic imbalance was identified in 16 of 54 cases (30%). Allelic imbalances of loci mapped to 7q were ob served in 15 of the 16 cases. The allelic imbalances were classified a s losses in 15 tumors (28%) and as gains in 1 (2%) by comparative mult iplex PCR analysis. The most common site of allelic loss included loci D7S523 and D7S486 at 7q31.1. A comparison with clinicopathological fe atures of the tested tumors revealed that the allelic loss of 7q31.1 c orrelated with higher tumor grade (P = 0.012) and lymph node metastasi s (P = 0.017). These results indicate that 7q31 may be the site of a p utative suppressor gene(s) important for the pathogenesis of prostate carcinoma, and that the genetic alterations at 7q31.1 may participate in tumor progression and metastasis.