title: Germline MYH mutations in a clinic-based series of Canadian multiple colorectal adenoma patients.
abstract: OBJECTIVE
  MYH is a member of the DNA base excision repair (BER) pathway and mutations of this gene predispose to the development of colorectal neoplasia in an autosomal recessive transmission pattern. Our objective was to determine the significance of MYH mutations in a series of Canadian patients with multiple adenomas.
  
  
  METHODS
  We screened for germline MYH mutations (by dHPLCO) in 20 clinic-based multiple adenoma patients who were adenomatous polyposis coli (APC) mutation-negative. Suspected mutations were confirmed by sequence analysis.
  
  
  RESULTS
  Six of 20 (30%) patients carried pathogenic biallelic MYH mutations, 1 Y165C homozygote and 5 compound heterozygotes of other sequence variants. We identified three novel variants, Q377X, 1314delA, and P281L, which are likely pathogenic. Twenty-nine relatives of the Y90X/1103delC compound heterozygous carrier were also screened for germline MYH mutations, and 1 homozygous and 14 heterozygous carriers were identified.
  
  
  CONCLUSIONS
  Among patients with multiple adenomas, biallelic MYH mutations account for approximately 30% of APC mutation negative cases and two thirds of these carry mutations other than the "common" Y165C and G382D variants. Clinical screening algorithms which focus only on the Y165C and G382D alleles are inadequate since additional pathogenic mutations may be identified by screening the entire gene.
authors.affiliation: Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Marina E
authors.initials: ME
authors.lastname: Croitoru
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
authors.forename: Terri
authors.initials: T
authors.lastname: Berk
authors.forename: Nando
authors.initials: N
authors.lastname: Di Nicola
authors.forename: Ilana
authors.initials: I
authors.lastname: Kopolovic
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D004273:DNA, Neoplasm; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase