Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/92141
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Type: Journal article
Title: Germline mutations in the polyposis-associated genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 are not common in individuals with Serrated Polyposis Syndrome
Author: Clendenning, M.
Young, J.
Walsh, M.
Woodall, S.
Arnold, J.
Jenkins, M.
Win, A.
Hopper, J.
Sweet, K.
Gallinger, S.
Rosty, C.
Parry, S.
Buchanan, D.
Citation: PLoS One, 2013; 8(6):e66705-1-e66705-5
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Mark Clendenning, Joanne P. Young, Michael D. Walsh, Sonja Woodall, Julie Arnold, Mark Jenkins, Aung Ko Win, John L. Hopper, Kevin Sweet, Steven Gallinger, Christophe Rosty, Susan Parry, Daniel D. Buchanan
Abstract: BACKGROUND: Recent reports have observed that individuals with serrated polyps, some of whom meet the clinical diagnostic criteria for Serrated Polyposis Syndrome (SPS), are among those who carry germline mutations in genes associated with polyposis syndromes including; (1) genes known to underlie hamartomatous polyposes (SMAD4, BMPR1A, and PTEN), (2) MUTYH-associated polyposis and (3) GREM1 in Hereditary Mixed Polyposis Syndrome (HMPS). The aim of this study was to characterise individuals fulfilling the current WHO criteria for SPS for germline mutations in these polyposis-associated genes. METHODS: A total of 65 individuals with SPS (fulfilling WHO criteria 1 or 3), were recruited to the Genetics of Serrated Neoplasia study between 2000 and 2012, through multiple Genetics or Family Cancer Clinics within Australia, or from the New Zealand Familial Gastrointestinal Cancer Service. Individuals with SPS were tested for coding mutations and large deletions in the PTEN, SMAD4, and BMPR1A genes, for the MUTYH variants in exons 7 (Y179C) and 13 (G396D), and for the duplication upstream of GREM1. RESULTS: We found no variants that were likely to be deleterious germline mutations in the SPS cases in the PTEN, SMAD4, and BMPR1A genes. A novel variant in intron 2 (c.164+223T>C) of PTEN was identified in one individual and was predicted by in silico analysis to have no functional consequences. One further individual with SPS was found to be mono-allelic for the MUTYH G396D mutation. No individuals carried the recently reported duplication within GREM1. CONCLUSIONS: Genes involved in the gastrointestinal hamartomatous polyposis, Hereditary Mixed Polyposis Syndrome and MUTYH-associated polyposis syndromes are not commonly altered in individuals with SPS.
Keywords: Humans; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; DNA Glycosylases; Intercellular Signaling Peptides and Proteins; Gene Duplication; Sequence Deletion; Germ-Line Mutation; Introns; Exons; Adult; Aged; Middle Aged; Female; Male; PTEN Phosphohydrolase; Smad4 Protein; Bone Morphogenetic Protein Receptors, Type I
Rights: © 2013 Clendenning et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030012014
DOI: 10.1371/journal.pone.0066705
Appears in Collections:Medicine publications

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