title: Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.
authors.affiliation: Laboratorio de Oncología Molecular, Hospital Clinico San Carlos, Martin Lagos s/n, Madrid 28040, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez de Abajo
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosar
authors.forename: Javier
authors.initials: J
authors.lastname: Godino
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Fernández
authors.forename: Jose-Lopez
authors.initials: JL
authors.lastname: Asenjo
authors.forename: Beatriz-Perez
authors.initials: BP
authors.lastname: Villamil
authors.forename: Pedro-Perez
authors.initials: PP
authors.lastname: Segura
authors.forename: Eduardo
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldes
mesh_terms: D020137:Base Pair Mismatch; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D013030:Spain
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein