Abstract 1683: Mutational landscape of colorectal cancer with POLE gene mutation

Abstract

Introduction POLE-mutated tumor is a rare subtype of colorectal cancer (POLE-CRC) and has been poorly understood because of its rarity. In this study, we have investigated the clinical and genetic features of POLE-CRC in the largest cohort of this unique subtype of CRC. Methods We included a total of 3,240 patients who had been treated at the Cancer Institute Hospital of Japanese Foundation for Cancer Research between 2004 and 2017, which were screened for POLE mutations, either by targeted-panel sequencing (n=544) or amplicon-based deep sequencing (n=2,696). POLE mutation-positive samples were further analyzed by whole exome sequencing. Results In total, 74 POLE variants were detected in 69 samples, of which 40 showed prominent hypermutation (median; 5,346, range; 837-16,990) with the predominance of COSMIC signature 10 associated with defective POLE functions. Patients with POLE-CRC were significantly younger (median; 50, range; 33-84), compared with those with non-hypermutated CRC (median; 65, p-value Conclusions Similar to MSI-CRC, POLE-CRC shows a favorable prognosis, where the mutations affecting APM are positively selected to evade immune surveillance, suggesting a possible role of checkpoint blockade in its therapeutics. Citation Format: Yoshikage Inoue, Nobuyuki Kakiuchi, Kenichi Yoshida, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Tetsuichi Yoshizato, HIroko Tanaka, Satoshi Nagayama, Satoru Miyano, Yoshiharu Sakai, Seishi Ogawa. Mutational landscape of colorectal cancer with POLE gene mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1683.