Hyperplastic Polyps and Sessile Serrated Adenomas as a Phenotypic Expression of MYH-Associated Polyposis

Clinical utility gene card for: MUTYH-associated polyposis (MAP), Autosomal recessive colorectal adenomatous polyposis, Multiple colorectal adenomas, Multiple adenomatous polyps (MAP) - update 2012

“…Since hyperplastic polyps and sessile serrated adenomas are a common finding in MAP and the occurrence of CRC in the absence of colorectal polyps has been described, the clinical presentation might be misdiagnosed as hyperplastic polyposis or sporadic CRC in some patients. 7,12 Phenotypic overlap with Lynch syndrome/ HNPCC has also been reported. 13 The frequency of biallelic MUTYH mutations is low (0.3-1.7%) in population-based and early-onset CRC cohorts and in patients with a low number of adenomas (o10) at any age, without an overt family history (and no carcinoma).…”

S3-Leitlinie – Kolorektales Karzinom

“…Das phänotypische Spektrum der MAP ist noch nicht abschließend geklärt: Einige große populationsbasierte Studien an KRK-Patienten zeigten, dass bis zu ein Drittel der biallelen MUTYH-Mutationsträger ein KRK ohne kolorektale Polypen entwickelt [269]. Daneben wurden bei bis zu 50 % der MAP-Patienten hyperplastische Polypen beschrieben [270].…”

Oxidative DNA damage drives carcinogenesis in MUTYH-associated-polyposis by specific mutations of mitochondrial and MAPK genes

“…27,28 Therefore, their coexistence, although very likely in different cellular subclones, might represent a peculiar feature of MUTYHassociated-polyposis carcinogenesis. Boparai and coworkers 6 reported that about 50% of MUTYHassociated-polyposis patients, besides adenomas with APC somatic mutation, show hyperplastic polyps and sessile serrated adenomas harbouring KRAS c.34G4T mutations. On the other hand, BRAF mutations are known to identify the subset of colorectal cancers following the serrated neoplastic pathway.…”

“…4,5 Although clinically variable, MUTYH-associatedpolyposis phenotype resembles that of APC-linked attenuated familial polyposis with the onset in the fourth-fifth decade of life, a limited number of adenomas (generally 30-100) and an increased susceptibility to colorectal cancer. However, unlike attenuated familial adenomatous polyposis, hyperplastic and sessile serrated polyps can develop; 6,7 in addition, approximately 60% of patients with polyposis have colorectal cancer at presentation. 8 Colorectal cancer cells of MUTYH-associatedpolyposis patients contain an excess of c.34 G4T transversions in KRAS gene; this is due to failure to repair mismatches induced by 8-oxo-guanine (8-oxoG) variant base, a widely recognized hallmark of oxidative stress.…”