Young J, Leggett B, Gustafson C, Ward M, Searle J, Thomas L, Buttenshaw R, Chenevix-Trench G
Glaxo Gastroenterology Laboratory, Clinical Research Centre, Brisbane, Australia.
Hum Mutat. 1993;2(5):351-4. doi: 10.1002/humu.1380020505.
Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas.
基因组不稳定表现为短串联重复序列（STR）位点存在额外等位基因，最近在遗传性非息肉病性结直肠癌（HNPCC）患者的结直肠肿瘤以及一些散发性肿瘤中被观察到。这些肿瘤被称为复制错误阳性（RER+）。在本研究中，我们证实了一部分未经选择的结直肠癌存在基因组不稳定，但未发现腺瘤存在不稳定的证据。我们进一步报告了四核苷酸序列以及两个肿瘤抑制基因内STRs的复制错误。对108例结直肠腺癌和46例腺瘤分析了4 - 15个微卫星标记处的变异条带。7例（6.5%）癌为RER+，其中4例起源于近端结肠。对腺瘤以及来自4例患者的配对腺瘤 - 癌和癌 - 转移样本分析表明，复制错误可能发生在癌的发生过程中，但在腺瘤中很少见。
