title: Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH.
abstract: OBJECTIVE
  Hyperplastic polyposis syndrome (HPS) is defined phenotypically with multiple, large and/or proximal hyperplastic polyps. There is no known germ-line predisposition. We aimed to characterize the clinicopathologic features of 38 patients with HPS and explore the role of germ-line mutations in the base excision repair genes MBD4 and MYH.
  
  
  METHODS
  Utilizing clinical databases of The Royal Melbourne Hospital Bowel Cancer Surveillance Service and the Familial Cancer Clinic, 38 patients with HPS were recruited. The patients were analyzed for age at first diagnosis, features of hyperplastic polyposis, family histories of polyposis and colorectal cancer (CRC), coexisting adenomas, serrated adenomas, incidence of CRC, and microsatellite instability in the tumours. Mutation analysis of MBD4 and MYH were performed.
  
  
  RESULTS
  Serrated adenomas were common (26%), and 19 (50%) of the 38 patients had a first-degree relative with CRC. Family history of HPS was uncommon, with only 2 cases found. Ten patients developed CRC, and 3 required surgery for polyposis. No pathogenic mutations in MBD4 were detected in the 27 patients tested, but 6 single nucleotide polymorphisms of uncertain functional significance were identified. Pathogenic biallelic MYH mutations were detected in 1 patient.
  
  
  CONCLUSIONS
  Mutations in MBD4 are unlikely to be implicated in HPS; MYH mutations should be studied, especially when adenomas occur in the same patient. The clinical, histopathologic, and molecular findings of this study should contribute to our understanding of HPS and its relationship to the serrated neoplasia pathway.
authors.affiliation: Familial Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia. elizabeth.chow@fmc.sa.gov.au
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chow
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.forename: Elly
authors.initials: E
authors.lastname: Lynch
authors.forename: Rebecca
authors.initials: R
authors.lastname: D'Souza
authors.forename: Clelia
authors.initials: C
authors.lastname: Aragona
authors.forename: Lindy
authors.initials: L
authors.lastname: Hodgkin
authors.forename: Gregor
authors.initials: G
authors.lastname: Brown
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Melissa
authors.initials: M
authors.lastname: Barker
authors.forename: Daniel
authors.initials: D
authors.lastname: Buchanan
authors.forename: Shannon
authors.initials: S
authors.lastname: Cowie
authors.forename: Steve
authors.initials: S
authors.lastname: Nasioulas
authors.forename: Desiree
authors.initials: D
authors.lastname: du Sart
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Barbara
authors.initials: B
authors.lastname: Leggett
authors.forename: Jeremy
authors.initials: J
authors.lastname: Jass
authors.forename: Finlay
authors.initials: F
authors.lastname: Macrae
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000483:Alleles; D001706:Biopsy; D003113:Colonoscopy; D045647:DNA Glycosylases / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase