title: Frequency of the common germline MUTYH mutations p.G396D and p.Y179C in patients diagnosed with colorectal cancer in Southern Brazil.
abstract: BACKGROUND
  MUTYH-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome associated with the development of colorectal tumors and colonic polyps at an early age. MAP syndrome is associated to germline biallelic mutations in the MUTYH gene which lead to deficient DNA repair through the base-excision repair system and accumulation of G:C→T:A transversions. Occurrence of such mutations in oncogenes and tumor suppressor genes drives colorectal carcinogenesis and is associated with the development of colonic polyps. Two common mutations, p.Y179C and p.G396D, are present in approximately 70-80% of MAP in European families with identified MUTYH germline mutations. The aim of this study was to assess the frequency of the germline MUTYH mutations p.Y179C and p.G396D in Brazilian patients with MAP and other hereditary colorectal cancer (CRC) phenotypes, as well as in sporadic CRC cases.
  
  
  METHODS
  A total of 75 patients were included. Samples were screened for the MUTYH germline mutations p.Y179C and p.G396D by allelic discrimination assays using allele-specific TaqMan® probes. In all mutation-positive cases, results were confirmed by sequencing.
  
  
  CONCLUSIONS
  Biallelic germline MUTYH mutations were identified in 4 of 60 (6.6%) patients with a phenotype of hereditary colorectal cancer. Germline MUTYH mutation screening should be considered in the differential diagnosis of hereditary colorectal syndromes, and not only in MAP, but also in familial adenomatous polyposis and Bethesda criteria-positive families. Additional mutation screening studies of the MUTYH gene in a larger number of Brazilian patients will be necessary to confirm these results and determine the validity and applicability of MUTYH mutation screening in our population.
authors.affiliation: Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre HCPA, Porto Alegre, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Pitroski
authors.forename: Silvia Liliana
authors.initials: SL
authors.lastname: Cossio
authors.forename: Patrícia
authors.initials: P
authors.lastname: Koehler-Santos
authors.forename: Marcia
authors.initials: M
authors.lastname: Graudenz
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Prolla
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D001938:Brazil; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase