Abstract 5385: Colorectal cancer methylome and laterality

Abstract

Abstract Background: Colorectal cancers are anatomically derived from Midgut area (from cecum to mid transverse colon) and Hindgut area (from mid transverse to anal canal). The laterality of colorectal cancers was reported as one of the prognosis markers of these cancers. Midgut originated cancers had statistically poorer overall survivals than Hind gut (Yahagi et al, J Gastrointest Surg, 2016). In addition to clinical reasons, for example its symptomless nature of the bowel obstruction on the right side, the difference of genetic and/or epigenetic profiles between both side colorectal cancers may exists. Methods: Surgically resected 30 colorectal cancers (Midgut n=9, Hidgut n=21) were included. Any clinicopathological factors except for tumor site was not statistically different between 2 groups. We decided to focus on colon cancer methylome and laterality in this study. Two novel methylation markers of colon cancers (PAX5 and VGF) which were extracted from microarray analysis were used, and quantitative methylation-specific PCR (QMSP) assay was performed for each marker.Results: Both PAX5 and VGF methylations were extremely tumor-specific markers (P<0.001 and P=0.011). Interestingly, Both markers tended to have high methylation frequency in Midgut derived cancers. High frequency of PAX5 promoter methylation was found in 9/9 cases (100%) of Midgut and 15/21 cases (71%) of Hindgut (P=0.141), while that of VGF was found in 6/9 cases (67%) of Midgut and 4/21 cases (19%) of Hindgut (P=0.030). In addition, three multiple colon cancers were found in the cohort. All of them were derived from Midgut area (T1/T1, T3/Tis and T3/Tis), and had high frequency of both PAX5 (2/3, 67%) and VGF (3/3, 100%) methylation. Conclusion: Cancer methylome between Midgut and Hindgut seemed to be different, and it may affect tumor malignancy, plurality and chemotherapy sensitivity. Now we are in progress of increased colorectal cancer cases (over 100) and methylation markers. Citation Format: Sho Hirabayashi, Masamichi Hayashi, Goro Nakayama, Keisuke Kurimoto, Hiroshi Tanabe, Mitsuro Kanda, Hideki Takami, Yukiko Niwa, Naoki Iwata, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Hiroyuki Sugimoto, Masahiko Koike, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera. Colorectal cancer methylome and laterality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5385. doi:10.1158/1538-7445.AM2017-5385