Takahashi S, Shan A L, Ritland S R, Delacey K A, Bostwick D G, Lieber M M, Thibodeau S N, Jenkins R B
Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Res. 1995 Sep 15;55(18):4114-9.
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 associated 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 7q31.1. A comparison with clinicopathological features of the tested tumors revealed that the allelic loss of 7q31.1 correlated with higher tumor grade (P = 0.012) and lymph node metastasis (P = 0.017). These results indicate that 7q31 may be the site of a putative 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.
细胞遗传学分析表明,7q22 - 32染色体区域在前列腺腺癌中常发生改变。此外,在最近的荧光原位杂交研究中,我们观察到7号染色体非整倍体在前列腺癌中很常见,并且与更高的肿瘤分级、晚期病理分期和早期前列腺癌死亡相关。这些发现表明,7号染色体的基因改变在前列腺癌的发生发展中起重要作用。为了更好地界定7号染色体的改变,我们对54对前列腺癌和对照DNA进行了21个微卫星位点的PCR分析。总体而言,在54例病例中有16例(30%)检测到7号染色体等位基因失衡。在这16例病例中的15例观察到定位于7q的位点存在等位基因失衡。通过比较多重PCR分析,15个肿瘤(28%)的等位基因失衡被归类为缺失,1个肿瘤(2%)为获得。等位基因缺失最常见的位点包括7q31.1处的D7S523和D7S486位点。与受试肿瘤的临床病理特征比较显示,7q31.1的等位基因缺失与更高的肿瘤分级(P = 0.012)和淋巴结转移(P = 0.017)相关。这些结果表明,7q31可能是一个对前列腺癌发病机制很重要的假定抑癌基因所在位点,并且7q31.1处的基因改变可能参与肿瘤进展和转移。