Low prevalence of germline hMSH6mutations in colorectal cancer families from Spain

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 37; pp. 5770 - 5776
• Main Author: Ana Sánchez de Abajo Miguel de la Hoya Alicia Tosar Javier Godino Juan Manuel Fernández Jose Lopez Asenjo Beatriz Perez Villamil Pedro Perez Segura Eduardo Diaz-Rubio Trinidad Caldes
• Format: Journal Article
• Language: English
• Published: 2005
• Subjects: hMSH6; 基因突变; 直肠癌; 结肠癌; 西班牙; 遗传因素
• ISSN: 1007-9327; 2219-2840

AIM： To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2. METHODS： We used PCR-based DGGE assay and direct sequencing to screen for hMSH6 gene in 91 HNPCC families. RESULTS： we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort, 8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations. CONCLUSION： Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.