Abstract 4688: Landscape of DNA copy number alterations of stage III colon cancer in the ACTS-CC trial (TRICC0706), a phase III trial of adjuvant chemotherapy with S-1 and UFT/LV in Japan: A comparison with Western data.
Authors: Toshiaki Ishikawa, Hiroyuki Uetake, Takashi Kobunai, Megumi Ishiguro, Shigeyuki Matsui, Kenichi Sugihara
Journal: Cancer Research (2013)

Abstract Background: The ACTS-CC trial is a phase III study of 1535 patients, designed to validate the noninferiority of S-1 to UFT/LV as adjuvant chemotherapy for stage III colon cancer. A genome-wide analysis of DNA copy number alterations was performed prospectively to identify predictive biomarkers and prognostic biomarkers. To accurately compare results between Japanese and Western clinical trials, it is important to investigate biological differences between Japanese and Western patients. Purpose: To elucidate DNA copy number alteration profiles of stage III colon cancer in Japan as compared with those in Western countries. Methods: Genomic DNA was extracted from 779 formalin-fixed, paraffin-embedded specimens. After quality assessment by arbitrary primed PCR, 162 samples were analyzed by high-density single-nucleotide polymorphism arrays (Affymetrix Human 250K StyI) according to the manufacturer's protocol. Copy number alterations in colon cancer in our study, estimated using a circular binary segmentation model, were compared with those of publically available data for colorectal or various other cancers in Western countries. First, concordance of the copy number gain or loss of each cytogenetic band with meta-analysis data reported by Diep et al. (Genes Chromosomes Cancer, 2006) was assessed by weighted kappa statistics. Next, copy number alterations of 43 focused cancer-related genes (APC, BRCA1, DCC, EGFR, FGFR2, MET, hMSH2, TP53, PTEN, etc.) were compared with those of 19 cancer subtypes (3131 cancer specimens) as reported by Beroukhim et al. (Nature, 2010) Results: Changes occurring in at least 15% of cases were losses of 4, 5q, 8p, 15q, 17p, and 18q and gains of 7, 8q, 13, and 20. Loss of 18q was seen in 80% of samples. Over 700 colon cancer data in Western countries retrieved from a meta-analysis were compared with our results according to each cytogenetic position (total 193 cytogenetic bands). Weighted kappa statistics, 0.83, indicated that the copy number profiles agreed closely between Japan and Western countries. Moreover, the strongest correlations of copy number profiles for 43 focused genes were seen between our results and colorectal cancers in Western countries, among various cancer subtypes. Conclusions: This is a preplanned analysis; eventually, clinical outcomes will be combined with biomarker analysis. Somatic copy number alteration profiles of stage III colon cancer in the ACTS-CC trial in Japan closely agreed with the results of previous Western studies. Our findings will facilitate understanding the characteristics of colon cancer in Japan and extrapolation of the results of Japanese phase III trials to Western countries. Citation Format: Toshiaki Ishikawa, Hiroyuki Uetake, Takashi Kobunai, Megumi Ishiguro, Shigeyuki Matsui, Kenichi Sugihara, ACTS-CC Trial Study Group. Landscape of DNA copy number alterations of stage III colon cancer in the ACTS-CC trial (TRICC0706), a phase III trial of adjuvant chemotherapy with S-1 and UFT/LV in Japan: A comparison with Western data. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4688. doi:10.1158/1538-7445.AM2013-4688