Mutation Profiling of Premalignant Colorectal Neoplasia.

Mutation Profiling of Premalignant Colorectal Neoplasia. Gastroenterol Res Pract. 2019;2019:2542640 Authors: Karczmarski J, Goryca K, Pachlewski J, Dabrowska M, Pysniak K, Paziewska A, Kulecka M, Lenarcik M, Mroz A, Mikula M, Ostrowski J Abstract Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequenci...
Source: Gastroenterology Research and Practice - Category: Gastroenterology Tags: Gastroenterol Res Pract Source Type: research