Abstract
AimsLittle is known about the molecular features of visible polyps with low-grade intestinal-type dysplasia in patients with inflammatory bowel disease (IBD). To better understand their origins and biological potential, we sought to genomically profile these lesions and compare them with invisible low-grade dysplasia and sporadic adenomas from non-IBD patients.Methods22 polyps within areas of colitis, 13 polyps outside areas of colitis, 10 foci of invisible dysplasia from patients with IBD and 6 sporadic tubular adenomas from non-IBD patients were analysed using the OncoPanel assay.ResultsPolyps arising in areas of colitis showed a greater spectrum of mutations, includingAPC,KRAS,FBXW7,TP53,ARID1AandTCF7L2. Polyps outside colitis and non-IBD sporadic adenomas showed a limited mutational profile, withAPCandCTNNB1mutations. Invisible dysplasia was characterised byTP53,CTNNB1andKRASalterations. Compared with dysplastic polyps, none of the invisible dysplastic foci showedAPCalterations (73%—within colitis; p=0.0001, 92%—outside colitis; p<0.0001, 83%—sporadic adenomas; p=0.001).TP53mutations were significantly higher in invisible dysplasia (50%) compared with polyps within colitis (9%; p=0.02) and outside colitis (8%; p=0.03).ConclusionsMolecular alterations in visible low-grade dysplastic polyps with conventional intestinal-type dysplasia from patients with IBD and sporadic adenomas from non-IBD patients overlap significantly.APCalterations appear to play a major role in the development of visible low-grade dysplastic lesions in patients with IBD, regardless of background colitis. As with IBD-associated colorectal cancers,TP53mutations are an early event in the development of invisible, low-grade conventional intestinal-type dysplasia in patients with IBD.