title: MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps.
abstract: OBJECTIVE
  MYH-associated polyposis is a recently described disease that is characterized by multiple colorectal adenomas and a recessive pattern of inheritance. Individuals with MYH-associated polyposis have biallelic mutations in MYH, a base excision repair gene, and are negative for germline mutations in the APC gene. In this study, the 2 most prevalent MYH mutations in white persons, Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3 groups: 400 undergoing screening colonoscopy and found to have 0-3 polyps, 444 with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which a germline mutation was not identified.
  
  
  METHODS
  Genotyping for Y165C and G382D was performed by Pyrosequencing.
  
  
  RESULTS
  Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0-3 polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n = 26), or in those with CRC who were older than 50 years (n = 328). Furthermore, these 2 MYH mutations were not found among patients whose tumors showed the presence of defective DNA mismatch repair (n = 62). However, the presence of biallelic germline MYH mutations correlated with the presence of >or=20 adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at 50 years of age or younger also presented with biallelic germline mutations in MYH.
  
  
  CONCLUSIONS
  These data suggest that screening of MYH should be considered not only in patients with multiple polyps but also in patients with early-onset CRC.
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Linnea M
authors.initials: LM
authors.lastname: Baudhuin
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Boardman
authors.forename: Kelle J
authors.initials: KJ
authors.lastname: Steenblock
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
authors.forename: Amy J
authors.initials: AJ
authors.lastname: French
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Johnson
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Burgart
authors.forename: Kari
authors.initials: K
authors.lastname: Rabe
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D017491:Genes, APC / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase