Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH.
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.
Chow
Elizabeth
E
Familial Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia. elizabeth.chow@fmc.sa.gov.au
Lipton
Lara
L
Lynch
Elly
E
D'Souza
Rebecca
R
Aragona
Clelia
C
Hodgkin
Lindy
L
Brown
Gregor
G
Winship
Ingrid
I
Barker
Melissa
M
Buchanan
Daniel
D
Cowie
Shannon
S
Nasioulas
Steve
S
du Sart
Desiree
D
Young
Joanne
J
Leggett
Barbara
B
Jass
Jeremy
J
Macrae
Finlay
F
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
D004273:DNA, Neoplasm; D004706:Endodeoxyribonucleases; C118712:MBD4 protein, human; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase