Okamura S, Koyama K, Miyoshi Y, Monden M, Takami M
Department of Medical Genetics, Osaka University Medical School, Suita, Japan.
J Hum Genet. 1998;43(2):143-5. doi: 10.1007/s100380050057.
We screened for germline mutations of mismatch repair genes, hMLH1 and hMSH2, in five Japanese families carrying hereditary nonpolyposis colorectal cancer (HNPCC) and in a patient with multiple primary cancers. Screening the entire coding regions of both genes using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we found two novel germline mutations in hMSH2. One was a 1-bp insertion in exon 12, detected in a patient who had undergone surgery six times for independent tumors (four primary colorectal carcinomas, a small intestinal carcinoma, and an endometrial cancer). The other, in a second patient, was a missense mutation from CTT to TTT at codon 390 in exon 7 that resulted in substitution of phenylalanine for leucine. This conservative alteration was not found in any of 50 normal controls, but we cannot exclude the possibility that it may represent a rare polymorphism rather than a factor in the disease.
我们在五个患有遗传性非息肉病性结直肠癌（HNPCC）的日本家族以及一名患有多种原发性癌症的患者中，筛查错配修复基因hMLH1和hMSH2的种系突变。通过聚合酶链反应-单链构象多态性（PCR-SSCP）分析筛查这两个基因的整个编码区，我们在hMSH2中发现了两个新的种系突变。一个是外显子12中的1个碱基插入，在一名因独立肿瘤接受过六次手术的患者中检测到（四次原发性结直肠癌、一次小肠癌和一次子宫内膜癌）。另一个在第二名患者中，是外显子7中第390密码子处从CTT到TTT的错义突变，导致亮氨酸被苯丙氨酸取代。在50名正常对照中均未发现这种保守性改变，但我们不能排除它可能代表一种罕见多态性而非疾病因素的可能性。
