P844 NGS to investigate genetic predisposition to colon cancer in patients with colon cancer over inflammatory bowel disease

• Published in: Journal of Crohn's and colitis 2018-01, Vol.12 (supplement_1), p.S543-S543
• Main Authors: Biscaglia, G, Latiano, A, Castellana, S, Bossa, F, Scimeca, D, Gentile, A, Latiano, T, Corritore, G, Nardella, M, Martino, G, Mazza, T, Andriulli, A, Palmieri, O
• Format: Article
• Language: English
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.971

Abstract Background Inflammatory bowel diseases (IBD) represent an important risk factor in the development of colorectal cancer (CRC). Strong evidences suggest CRC occurs in the inflamed epithelium, according to the sequence dysplasia-carcinoma, with an increasing risk after 8–10 years since IBD diagnosis. To date, more than 200 loci have been associated to IBD predisposition, none to IBD-related cancer development. The aim of this study is to identify mutations in oncogenes and protoncogenes and their contribute to clarify the way that leads IBD patients to CRC. Methods We profiled a panel of 40 genes potentially involved in cancers predisposition. A germline variant identification analysis pipeline was performed on the DNA of individuals with CRC diagnosis and IBD history. We ranked all identified germline mutations by pathogenicity and summarised the allelic frequencies of pathogenic variants and of uncertain clinical significance (VUS). NOD2 status was analysed too. Results We identified 25 CRC patients with history of IBD (mean age at IBD diagnosis 43 years, range 25–72; mean age at CRC diagnosis 62 years, range 36–72), all enrolled in a single referral center. Multigene panel testing identified mutations in 16 IBD patients (64%): 3 encompassing MLH1 gene, 4 APC and the remaining in MUTYH, MSH2, MSH3, EPCAM, BRCA1, CHEK2, POLD1 and PDGFRA. Only in two cases (8%) the family history suggested a Lynch syndrome. IARC Class 1 or 2 were excluded. Six patients (24%) resulted carriers of at least one major NOD2 susceptibility mutations (one compound heterozygotes) and further 3 rare new variants. Conclusions This study of IBD-related CRC patients demonstrates a high rate of susceptibility mutations in genes involved in polyposis and in Mismatch Repair (MMR) pathways. Although further evaluations are needed, identifying genetic mutations in oncogenes and protoncogenes might be useful to stratify patients who will need an intensive surveillance regimen or an early indication to prophylactic colectomy.