Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients

查看全文 作　　者：Mohd Nizam [1]Zahary;Ravindran [1]Ankathi;Human Genome [1]Centre;Gurjeet [2]Kaur;Muhammad Radzi Abu [3]Hassan;Harjinder [4]Singh;Venkatesh R [5]Naik

机构地区：[1]School of Medical Sciences,University Sains Malaysia Health Campus,16150 Kubang Kerian,Kelantan,Malaysia;[2]Institute for Research in Molecular Medicine,University Sains Malaysia,11800 Penang,Malaysia;[3]Internal Medicine Department,Hospital Alor Star,05460 Alor Star,Kedah,Malaysia;[4]Department of Medicine,Hospital Queen Elizabeth,88586 Kota Kinabalu,Sabah,Malaysia;[5]Department of Pathology,School of Medical Sciences,University Sains Malaysia Health Campus,16150 Kubang Kerian,Kelantan,Malaysia

出　　处：《World Journal of Gastroenterology》索引2012年第18卷第8期,共7页

基　　金：Supported by USM Research University Grant, No. 1001/CIPPT/813005 摘　　要：AIM: To investigate the protein expression profi le of mismatch repair (MMR) genes in suspected cases of Lynch syndrome and to characterize the associated germline mutations. METHODS: Immunohistochemical analysis of tumor samples was performed to determine the protein expression profile of MMR protein. Germline mutation screening was carried out on peripheral blood samples. The entire exon regions of MLH1 and MSH2 geneswere amplifi ed by polymerase chain reaction, screened by denaturing high performance liquid chromatography (dHPLC) and analyzed by DNA sequencing to characterize the germline mutations. RESULTS: Three out of 34 tissue samples (8.8%) and four out of 34 tissue samples (11.8%) showed loss of nuclear staining by immunohistochemistry, indicating the absence of MLH1 and MSH2 protein expression in carcinoma cells, respectively. dHPLC analysis followed by DNA sequencing showed these samples to have germline mutations of MSH2 gene. However, no deleterious mutations were identifi ed in any of the 19 exons or coding regions of MLH1 gene, but we were able to identify MLH1 promoter polymorphism, -93G > A (rs1800734), in 21 out of 34 patients (61.8%). We identified one novel mutation, transversion mutation c.2005G > C, which resulted in a missense mutation (Gly669Arg), a transversion mutation in exon 1, c.142G > T, which resulted in a nonsense mutation (Glu48Stop) and splice-site mutation, c.2006-6T > C, which was adjacent to exon 13 of MSH2 gene. CONCLUSION: Germline mutations were identified in four Malaysian Lynch syndrome patients. Immunohistochemical analysis of tumor tissue proved to be a good pre-screening test before proceeding to germline mutation analysis of DNA MMR genes. 关键词：基因启动子突变分析胚系突变马来西亚综合征患者变性高效液相色谱 DNA测序

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Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients

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