Profiles of somatic mutations in tissue of IBD and IBD-associated carcinomas revealed by a targeted next-generation sequencing (NGS) tumour panel confirm notable differences from sporadic colorectal carcinomas
Abstract
Inflammatory bowel diseases (IBD) present an increased risk of developing colorectal carcinoma. Neutrophil-released chemicals in the immune response to inflammation causes mutagenesis, and its long-term effects may result in the development of tumour-specific DNA mutations that are the initiators of malignant conversion of intestinal tissue cells.
The subsequent molecular changes within the affected gastrointestinal mucosa induce focal changes of the tissue morphology. The molecular mechanisms of this malignant conversion show specific differences from similar mechanisms leading to other types of colorectal carcinoma.
The aim of the project is to trace tissue-specific somatic DNA mutations by massively parallel next-generation sequencing using an extensive panel of 50 carcinoma-associated genes (oncogenes and tumour suppressors). Furthermore, the purposes was to compare the resulting profiles obtained from IBD (Crohn's disease, Ulcerative colitis) and IBD-associated carcinomas to those obtained from tissue of sporadic colorectal tumours.