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.
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.
Authors: J M Cunningham; C Y Kim; E R Christensen; D J Tester; Y Parc; L J Burgart; K C Halling; S K McDonnell; D J Schaid; C Walsh Vockley; V Kubly; H Nelson; V V Michels; S N Thibodeau Journal: Am J Hum Genet Date: 2001-08-24 Impact factor: 11.025
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Authors: Barbara M Buttin; Matthew A Powell; David G Mutch; Sheri A Babb; Phyllis C Huettner; Tina Bocker Edmonston; Thomas J Herzog; Janet S Rader; Randall K Gibb; Alison J Whelan; Paul J Goodfellow Journal: Am J Hum Genet Date: 2004-04-19 Impact factor: 11.025
Authors: Paolo Peterlongo; Khedoudja Nafa; Gabriel S Lerman; Emily Glogowski; Jinru Shia; Tian Z Ye; Arnold J Markowitz; José G Guillem; Prema Kolachana; Jeffrey A Boyd; Kenneth Offit; Nathan A Ellis Journal: Int J Cancer Date: 2003-11-20 Impact factor: 7.396
Authors: Sanne M Petersen; Mette Dandanell; Lene J Rasmussen; Anne-Marie Gerdes; Lotte N Krogh; Inge Bernstein; Henrik Okkels; Friedrik Wikman; Finn C Nielsen; Thomas V O Hansen Journal: BMC Med Genet Date: 2013-10-03 Impact factor: 2.103