Herfarth K K, Kodner I J, Whelan A J, Ivanovich J L, Bracamontes J R, Wells S A, Goodfellow P J
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Genes Chromosomes Cancer. 1997 Jan;18(1):42-9. doi: 10.1002/(sici)1098-2264(199701)18:1<42::aid-gcc5>3.0.co;2-1.
The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. Microsatellite instability is also seen in 10-16% of sporadic colorectal cancers. A limited number of MSH2 and MLH1 mutations have been described for sporadic colorectal cancers. In this study, we screened 12 primary sporadic colorectal cancers with microsatellite instability for mutations in MSH2 and MLH1 by using reverse transcription-polymerase chain reaction (RT-PCR) and single-strand-conformation-variant (SSCV) analysis. Eight mutations were identified in six tumors. One mutation in MLH1 was found to be present in the patient's germline DNA. Four tumors had somatic mutations in MLH1, and, in two of these tumors, two different mutations were identified. A single tumor had a somatic MSH2 mutation. Our observations suggest that MLH1 is mutated more frequently than MSH2 in sporadic colorectal cancers with microsatellite instability.
微卫星不稳定性是遗传性非息肉病性结直肠癌（HNPCC）患者肿瘤的一个特征，它是DNA错配修复缺陷的结果。DNA错配修复基因MSH2和MLH1的突变可能占HNPCC家系的90%。微卫星不稳定性在10%-16%的散发性结直肠癌中也可见。对于散发性结直肠癌，已描述了有限数量的MSH2和MLH1突变。在本研究中，我们通过逆转录-聚合酶链反应（RT-PCR）和单链构象变异（SSCV）分析，对12例具有微卫星不稳定性的原发性散发性结直肠癌进行了MSH2和MLH1突变筛查。在6个肿瘤中鉴定出8个突变。在患者的生殖系DNA中发现了1个MLH1突变。4个肿瘤在MLH1中有体细胞突变，其中2个肿瘤鉴定出2种不同的突变。1个肿瘤有体细胞MSH2突变。我们的观察结果表明，在具有微卫星不稳定性的散发性结直肠癌中，MLH1的突变比MSH2更频繁。
