前列腺癌演进过程中的等位基因失衡

目的了解前列腺癌克隆演变(clonal evolution)过程中的遗传学机制。方法采用激光显微切割技术从保存的石蜡包埋组织中获取基因组DNA;利用6个位于染色体8p12-21、8p22、17q21上的具有多态性的微卫星标记,对25例患者原发癌及相应转移灶中等位基因的缺失或保留进行分析。结果在24例信息病例中,14例(58%)在原发癌及相应转移灶中所有位点均表现为相同的等位基因缺失或保留模式,而另外10例(42%)则显示不一致的等位基因缺失。10例中有8例原发癌表现为等位基因保留,而在相应转移灶则为缺失,另外2例在一个或一个以上的位点表现为不同的等位基因缺失模式。结论前列腺癌在原发癌及相应转移灶遗传组成上的差异可能与其内在异质性、整体遗传不稳定性及克隆差异有关。

Allelic Imbalance in the Clonal Evolution of Prostate Carcinoma

Objective To observe the genetic basis of the clonal evolution of prostate carcinoma. Methods The pattern of allelic loss in 25 matching primary and metastatic prostatic adenocarcinoma were analyzed. DNA sample for the analysis of allelic loss pattern were prepared by tissue microdissection. The oligonucleotide primer pairs for the microsatellite DNA markers were D8S133, D8S136, D8S137, ANK1 on chromosome 8p12-21, LPLTET on chromosome 8p22, and D17S855 on chromosome 17q21. Results The overall frequency of allelic imbalance was 79% in primary tumors and 88% in paired metastases. Of 24 informative cases, 14 patients(58%) showed the same pattern of allelic loss or retention in matching primary and metastatic tumor at all marker locus; discordant allelic loss was observed in the remaining 10 patients(42%). Four patients showed loss of the same allele at one or more marker loci and both primary and metastatic tumors, but discordant allelic loss was observed at other marker loci. Five patients showed allelic loss in at least one genetic marker in the metastatic tumor but not in its matching primary tumor. Five patients displayed loss in one or more marker loci in a primary tumor but not in the matching metastases. Conclusion These data suggest that different patterns of allelic deletion may be acquired during cancer progression to metastases. The differences in genetic composition between primary prostate carcinoma and its metastases may be related to intrinsic cancer heterogeneity, overall genetic instability, and clonal divergence.