P-225 Mutation detection rate among patients with adenomatous polyposis

Abstract

Introduction: There are two well-defined pathways for colorectal carcinogenesis, the suppressor and the mutator pathways. The suppressor pathway results from mutation in genes such as APC and MYH. These mutations are characteristic of hereditary polyposis colorectal cancer, known as familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP) and MYH-associated polyposis (MAP). Objective: This study retrospectively examines the mutation rate detection among patients assessed for APC and/or MYH mutation in routine clinical practice. Methods: Suppressor pathway does not possess distinctive clinical or pathologic features. We routinely assess patients with 20 or more colonic adenomas, regardless of age. From January 1st 2008 to December 31st 2014 we screened 48 cases fulfilling the 20 colonic adenomas cutoff. Each patient was screened for the presence of APC and/or MYH mutation using multiplex ligation-dependent probe amplification (MLPA), real time-polymerase chain reaction (RT-PCR) followed by high resolution melting technique (HRM). Positive HRM profiles were sequenced, with Big Dye Terminators in automatic genetic analyzer ABI 3130. Results: Mutations were detected in 3/40 cases (7.5%), not detected in 37/40 (92.5%). In the remaining 8 cases, the results are expected and they are excluded from statistical analysis. Conclusion: These results demonstrated a low mutation detection rate in APC and/or MYH gene among people with 20 or more adenomatous polyps. Since the economic impact of these molecular techniques, these data support the search of more restrictive criteria to assess mutation in APC and/or MYH gene.