Y Yuan1, S Zheng. 1. Cancer Institute, Zhejiang University, Hangzhou 310009.
Abstract
OBJECTIVE: To analyze the molecular characteristics of 29 ICG-HNPCC families and 34 suspected HNPCC families. METHODS: Genomic DNAs were prepared from peripheral blood samples of probands for DNA test. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of hMLH1 and hMSH2 genes. RESULTS: In 29 ICG-HNPCC families, 9 mutations in the hMLH1 gene were detected, while no mutation was found in the hMSH2 gene. The total mutation rate was 31.0% (9/29). In 34 suspected HNPCC families, 8 mutations in the hMLH1 gene and 2 mutations in the hMSH2 gene were detected. The total mutation rate in this group was 29.4% (10/34), including hMLH1 gene 23.5% (8/34) and hMSH2 gene 5.9% (2/34). hMLH1 gene was proven to be the main responsible gene in both ICG-HNPCC and suspected HNPCC families, and no obvious difference was found between the mutation rate in the two kinds of families (P > 0.05). As for the mutation type and location, similar characteristics were also detected. Almost all mutations located in the latter half of both genes, and mutation leading to protein truncation was the commonest type. CONCLUSION: The similarity of mutation rate, mutation type and mutation location between ICG-HNPCC and suspected HNPCC suggested the similarity of molecular basis and genetic background between these two groups, and also strongly indicated our criteria for suspected HNPCC is reasonable, and useful in the clinical diagnosis and management of HNPCC.
OBJECTIVE: To analyze the molecular characteristics of 29 ICG-HNPCC families and 34 suspected HNPCC families. METHODS: Genomic DNAs were prepared from peripheral blood samples of probands for DNA test. PCR-SSCP and DNA sequencing analysis were employed to screen the germline mutations of hMLH1 and hMSH2 genes. RESULTS: In 29 ICG-HNPCC families, 9 mutations in the hMLH1 gene were detected, while no mutation was found in the hMSH2 gene. The total mutation rate was 31.0% (9/29). In 34 suspected HNPCC families, 8 mutations in the hMLH1 gene and 2 mutations in the hMSH2 gene were detected. The total mutation rate in this group was 29.4% (10/34), including hMLH1 gene 23.5% (8/34) and hMSH2 gene 5.9% (2/34). hMLH1 gene was proven to be the main responsible gene in both ICG-HNPCC and suspected HNPCC families, and no obvious difference was found between the mutation rate in the two kinds of families (P > 0.05). As for the mutation type and location, similar characteristics were also detected. Almost all mutations located in the latter half of both genes, and mutation leading to protein truncation was the commonest type. CONCLUSION: The similarity of mutation rate, mutation type and mutation location between ICG-HNPCC and suspected HNPCC suggested the similarity of molecular basis and genetic background between these two groups, and also strongly indicated our criteria for suspected HNPCC is reasonable, and useful in the clinical diagnosis and management of HNPCC.