Frequent Loss of Heterozygosity at 7q31.1 in Primary Prostate Cancer Is Associated with Tumor Aggressiveness and Progression1

Cytogenetic analyses have demonstrated that chromosome region 7q22-32 is commonly altered in prostate adenocarcinomas. In addition, in recent fluorescence in situ hybridization studies, we have observed that aneusomy of chromosome 7 is frequent in prostate cancer and is associ ated with higher tumor grade, advanced pathological stage, and early prostate cancer death. These findings suggest that genetic alterations of chromosome 7 play a significant role in the development of prostate cancer. To better define the chromosome 7 alterations, PCR analysis of 21 microsatellite loci was performed on 54 paired prostate cancer and control DNAs. Overall, chromosome 7 allelic imbalance was identified in 16 of 54 cases (30% ). Allelic imbalances of loci mapped to 7q were observed in 15 of the 16 cases. The allelic imbalances were classified as losses in 15 tumors (28% ) and as gains in 1 (2% ) by comparative multiplex PCR analysis. The most common site of allelic loss included loci D7S523 and D7S486 at 7iI.H.I. A comparison with clinicopathological features of the tested tu mors revealed that the allelic loss of 7q31.1 correlated with higher tumor grade (/' = 0.012) and lymph node metastasis i/' = 0.017). These results indicate that 7q31 may be the site of a putative suppressor gene(s) impor tant for the pathogenesis of prostate carcinoma, and that the genetic alterations at 7q3l.l may participate in tumor progression and metastasis.