Department of Biochemistry, Institute of Medical Science, Jeju National University, Jeju 690-756, Korea.
BMB Rep. 2010 Oct;43(10):693-7. doi: 10.5483/BMBRep.2010.43.10.693.
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (F396I) combined with multiple missense mutations in MSH2 (D295G, K808E, Q855P, and I884T). The findings underline the importance of efficient pre-screening of conspicuous cases.
遗传性非息肉病性结直肠癌（HNPCC）是一种常染色体显性综合征，其特征是易发生早发癌症。HNPCC 是由错配修复基因 MLH1、MSH2、MSH6、PMS1 和 PMS2 中的杂合功能丧失突变引起的。我们对患有林奇综合征的患者和随后接受手术治疗的 11 名无亲缘关系的结直肠癌患者的 MLH1 和 MSH2 基因进行了基因分型。5 名林奇综合征患者携带 MLH1 或 MSH2 的种系突变。其中 2 人被鉴定为 MLH1 中的已知突变：外显子 10 的缺失和点突变（V384D）。其余 3 名患者表现出新的突变：MLH1 中的重复（937_942dupGAAGTT）；外显子 8、9 和 10 的缺失；以及 MLH1 中的点突变（F396I），同时 MSH2 中存在多个错义突变（D295G、K808E、Q855P 和 I884T）。这些发现强调了对明显病例进行有效预筛查的重要性。
