Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis

Karam S. Boparai, Evelien Dekker, Susanne van Eeden, Mirjam M. Polak, Joep F. W. M. Bartelsman, Elisbeth M. H. Mathus-Vliegen, Josbert J. Keller, Carel J. M. van Noesel

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Abstract

BACKGROUND & AIMS: 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
Original languageEnglish
Pages (from-to)2014-2018
JournalGastroenterology
Volume135
Issue number6
DOIs
Publication statusPublished - 2008

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