摘要
Lynch syndrome (LS),an autosomal dominantly inherited disease previously known as hereditary non-polyposis coloreetal cancer (HNPCC),leads to a high risk of colorectal cancer (CRC)as well as malignancy at certain sites including endometrium,ovary,stomach,and small bowel (Hampel et al.,2008;Lynch et al.,2009).Clinically,LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005).LS is associated with mutations of DNA mismatch repair (MMR)genes such as MLH1,MSH2, MSH6,PMS2,and EPCAM (Ligtenberg et al.,2009;Lynch et al.,2009),which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes.
目的:寻找一个Lynch综合征患者所在家系携带的DNA错配修复基因突变,探讨各突变对肿瘤发生发展的影响。创新点:MLH1的第19号外显子c.2250_2251insAA移码突变既往被认为是意义未名突变,而我们的研究为明确该突变的致病意义提供了依据。另外,我们首次报道了MLH3基因第1号外显子c.1397C>A突变。该突变有可能使Lynch综合征患者的发病年龄提前。方法:运用免疫组织化学技术检测家系先证者肿瘤组织中错配修复基因蛋白的缺失情况,使用二代测序技术通过先证者血标本明确患者所携带的突变。同时运用Sanger法检测家系其他成员该突变的携带情况以明确突变对肿瘤发生发展的影响。结论:我们在患者体内发现MLH1基因第19号外显子移码突变(c.2250_2251insAA)以及MLH3基因第1号外显子c.1397C>A突变。在患者家系中,我们仅检测到有MLH1突变,因此该突变极有可能为致病突变。
