title: No association between MUTYH and MSH6 germline mutations in 64 HNPCC patients.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumour predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. In contrast to MLH1 and MSH2, germline mutations in MSH6 are associated with a milder and particularly variable phenotype. Based on the reported interaction of the MMR complex and the base excision repair protein MUTYH, it was hypothesised that MUTYH mutations serve as phenotypical modifiers in HNPCC families. Recently, a significantly higher frequency of heterozygosity for MUTYH mutations among MSH6 mutation carriers was reported. We examined 64 MSH6 mutation carriers (42 truncating mutations, 19 missense mutations and 3 silent mutations) of the German HNPCC Consortium for MUTYH mutations by sequencing the whole coding region of the gene. Monoallelic MUTYH mutations were identified in 2 of the 64 patients (3.1%), no biallelic MUTYH mutation carrier was found. The frequency of MUTYH mutations was not significantly higher than that in healthy controls, neither in the whole patient group (P=0.30) nor in different subgroups regarding mutation type. Our results do not support the association between MSH6 mutations and heterozygosity for MUTYH mutations.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. v.steinke@uni-bonn.de
authors.forename: Verena
authors.initials: V
authors.lastname: Steinke
authors.forename: Nils
authors.initials: N
authors.lastname: Rahner
authors.forename: Monika
authors.initials: M
authors.lastname: Morak
authors.forename: Gisela
authors.initials: G
authors.lastname: Keller
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Heike
authors.initials: H
authors.lastname: Görgens
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Royer-Pokora
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
mesh_terms: D016022:Case-Control Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase