Genetic detection of Chinese hereditary nonpolyposis colorectal cancer

Abstract

AIM:To explore the germline mutations of the two main DNA mismatch repair genes (hMSH2 and hMLH1) between patients with hereditary non-polyposis colorectal cancer (HNPCC) and suspected (atypical) HNPCC. METHODS:Genomic DNA was extracted from the peripheral blood of the index patient of each family, and germline mutations of hMSH2 and hMLH1 genes were detected by PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. RESULTS:For PCR-SSCP analysis, 67% (4/6) abnormal exons mobility in typical group and 33% (2/6) abnormal exons mobility in atypical group were recognized. In direct DNA sequencing, 50% (3/6) mutation of MMR genes in typical group and 33% (2/6) mutation of MMR genes in atypical group were found, and 4/6 (66.67%) and 1/6 (16.67%) mutations of hMSH2 and hMLH1 were identified in typical HNPCC and atypical HNPCC, respectively. CONCLUSION:Mutation detection of the patients is of benefit to the analysis of HNPCC and, PCR-SSCP is an effective strategy to detect the mutations of HNPCC equivalent to direct DNA sequence. It seems that there exist more complicated genetic alterations in Chinese HNPCC patients than in Western countries.

Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal cancer patients

“…In some populations, such as Portuguese and Brazilian, most of the novel mutations were missense [22,23]. However, most of the novel mutations that were reported by Cui et al [30] were frameshift. In another study, Rey et al reported 6 novel mutations in MMR genes, 2 of which were in hMLH1.…”

Germline hMSH2 promoter mutation in a Chinese HNPCC kindred: evidence for dual role of LOH

“…All hMSH2 gene-coding regions and the exon/intron boundaries were PCR amplified and then bidirectionally sequenced. The primers used were designed previously (14) and were available upon request. Large genomic alterations in hMSH2 were screened by a modified multiplex PCR assay described previously (23).…”

“…From 1995 to 2004, we examined 61 suspected HNPCC families and identified pathogenic germline mutations in the coding regions of hMLH1 , hMSH2 , or hMSH6 (14, Yan H, Jin H, Xue G, Mei Q, Ding F, Hao L, Sun S‐H, unpublished data). To clarify whether the germline mutations in the promoter regions are implicated in the tumorigenesis of HNPCC, we subsequently screened the promoter regions of hMSH2 , hMLH1 , and hMSH6 in 37 suspected HNPCC families.…”

Microsatellite instability and novel mismatch repair gene mutations in northern Chinese population with Hereditary non‐polyposis colorectal cancer

“…There are very little data on the incidence and spectrum of the MMR gene mutation in HNPCC families from the northern Chinese population. Reports of germline MMR gene mutation in mainland China typically involved only a few families, and one or two larger series were derived from Shanghai, which was also composed of a southern Chinese population 12–15 . With the introduction of national birth control (the one child policy), the study of hereditary disease will become more and more difficult and there is a pressing need to systematically characterize the spectrum of the MMR gene mutation in HNPCC families in different ethnic groups of China, so as to facilitate the future design of a strategy for genetic diagnosis.…”