title: Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis.
abstract: OBJECTIVE
  MYH-associated polyposis (MAP) is a disorder caused by a bi-allelic germline MYH mutation, characterized by multiple colorectal adenomas. These adenomas typically harbor G:C-->T:A transversions in the APC and K-ras genes caused by MYH deficiency. Occasional hyperplastic polyps (HPs) have been described in MAP patients but a causal relationship has never been investigated. We examined the presence of HPs and sessile serrated adenomas (SSAs) in 17 MAP patients and studied the occurrence of G:C-->T:A transversions in the APC and K-ras gene in these polyps.
  
  
  METHODS
  MAP patients were analyzed for the presence of HPs/SSAs. APC-mutation cluster region and K-ras codon 12 mutation analysis was performed in adenomas (n = 22), HPs (n = 63), and SSAs (n = 10) from these patients and from a control group of sporadic adenomas (n = 17), HPs (n = 24), and SSAs (n = 17).
  
  
  RESULTS
  HPs/SSAs were detected in 8 of 17 (47%) MAP patients, of whom 3 (18%) met the criteria for hyperplastic polyposis syndrome. APC mutations were detected only in adenomas and comprised exclusively G:C-->T:A transversions. K-ras mutations were detected in 51 of 73 (70%) HPs/SSAs in MAP patients, compared with 7 of 41 (17%) sporadic HPs/SSAs in the control group (P < .0001). In HPs/SSAs, 48 of 51 (94%) K-ras mutations showed G:C-->T:A transversions, compared with 2 of 7 (29%) sporadic HPs/SSAs in the control group (P < .0001).
  
  
  CONCLUSIONS
  HPs and SSAs are a common finding in MAP patients. The detection of almost exclusively G:C-->T:A transversions in the K-ras gene of HPs/SSAs strongly suggests that these polyps are related causally to MYH deficiency. This implies that distinct pathways, that is, APC-gene related in adenomas and nonrelated in HPS/SSAs, appear to be operational in MAP.
authors.affiliation: Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Karam S
authors.initials: KS
authors.lastname: Boparai
authors.forename: Evelien
authors.initials: E
authors.lastname: Dekker
authors.forename: Susanne
authors.initials: S
authors.lastname: Van Eeden
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: Polak
authors.forename: Joep F W M
authors.initials: JF
authors.lastname: Bartelsman
authors.forename: Elisbeth M H
authors.initials: EM
authors.lastname: Mathus-Vliegen
authors.forename: Josbert J
authors.initials: JJ
authors.lastname: Keller
authors.forename: Carel J M
authors.initials: CJ
authors.lastname: van Noesel
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000483:Alleles; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003113:Colonoscopy; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC / Q000502:physiology; D011905:Genes, ras / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies
chemical_list: D004273:DNA, Neoplasm; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase