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P817 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

P. Minarikova*1, L. Benesova2, B. Belsanova2, A. Semyakina2, M. Kasalicky3, M. Bortlík4, M. Lukáš4, M. Zavoral1, M. Minarik1,2

1Military University Hospital and Charles University, Department of Internal Medicine, First Faculty of Medicine, Prague, Czech Republic, 2Genomac Research Institute, Center for Applied Genomics of Solid Tumours (CEGES), Prague, Czech Republic, 3Military University Hospital and Charles University, Surgical Clinic, Second Faculty of Medicine, Prague, Czech Republic, 4ISCARE, a.s., IBD centre, Prague, Czech Republic


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.


The group consisted of 25 patients with IBD and 5 patients with sporadic colorectal cancer covering samples from primary tumour, metastases with both MSI and MSS status. For each tumour DNA was extracted from either a biopsy or resected tissue (native or FFPE) and subjected to NGS performed on Illumina MiSeq sequencer using SureSeq™ Solid tumour hybridisation-based enrichment panel (Oxford Gene Technology, Oxfordshire, UK). NGS data were processed by NextGENe sequence analysis suite (Softgenetics, State College, PA).


We mapped the incidence and frequency of major control oncogenic mutations in tissue samples of IBD patients. In general, a difference was observed when comparing mutational spectra among IBD, IBD-associated carcinomas and sporadic carcinomas. As expected, we have confirmed an inverse succession of mutations affecting oncogenes and tumour-suppressors from traditional sporadic pathway. Furthermore, we have revealed a high incidence of somatic mutations of the NOTCH1 and EPAS1 genes, which have previously been shown to be related to their activation and inflammatory processes in the tissue.


Investigation of the presence of specific mutations in inflammatory tissue of IBD patients represents a qualitatively new approach to disease characterisation, including the prediction of the risk of malignant conversion. The study was supported by Czech Ministry of Defense research project MO1012.