765P - The nationwide cancer genome screening project in Japan SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced small intestine cancer

Abstract

Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. Methods: This study is ongoing with 20 major cancer centers. Patients with aNon-CRC, including who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutations, copy number variants (CNVs) and gene fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of advanced small intestine cancer cohort. Results: As of October 31st in 2016, a total of 36 advanced small intestine cancer samples were analyzed. The sequence was successfully performed in 26 tumors (72.2%). Out of 26 patients, the primary tumors are located in duodenum (n = 15), jejunum (n = 7), and ileum (n = 2), and unknown (n = 2). The frequently detected mutations in 26 samples of which results were available were KRAS (50.0%), TP53 (42.3%), and APC (23.1%). The frequently detected CNVs (≥ 7copies) were MDM2 (7.7%) and CDK6 (3.8%). PIK3CA mutations were identified in 4 cases (15.4%) and BRAF mutations were identified in 2 cases (7.7%). No gene fusion was detected. Conclusions: This nationwide screening system is efficient to detect rare gene alterations in advanced small intestine cancer. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial identification: UMIN000016344 Legal entity responsible for the study: SCRUM-Japan GI-SCREEN Funding: 15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC Disclosure: W. Okamoto: Research Funding from MSD. Y. Honma: Honoraria from Tenjin pharma. Speakers' bureau from Taiho, Nihon kayaku, Daiichi sankyo and Novartis. Research funding from Daiichi Sankyo, Astrazeneca, Merck serono, Novartis and Teijin pharma. T. Kudo: Research funding from Yakult Honsha, Chugai Pharma and Ono Pharma. Y. Komatsu: Honoraria from Novartis, Pfizer and Bayer. Speakers' bureau from Taiho, Lilly, Chugai, Merch, Novartis, Pfizer and Bayer. Research funding from Taiho, Lilly, MSD, Ono, Novartis, Bayer, Chugai and Yakult. H. Hara: Honoraria from Chugai, Taiho, Merck Serono, Yakult and Lilly. Consulting or advisory role from Ono and Chugai. Research funding from AstraZeneca, Chugai, Merck Serono, MSD, Ono, Taiho, Takeda, Boehringer Ingelheim, Daiichi Sankyo, Lilly, etc. D. Naruge: Research funding from Taiho, Ono, Onco Therapy Science, Merck, Zeria, Lilly, Takeda, Chugai, Bayer, Graxo Smith Kline, Yakult, Sumitomo Dainippom, Daiichi Sankyo, Novartis, Bristol-Myers, Sanofy, Kyowa Hakko Kirin, Astellas, Pfizer, Janssen. T. Moriwaki: Honoraria from Bayer, Chugai Pharma, Merck Serono, Novelpharma, Taiho Pharmaceutical, Takeda, and Yakult Honsha. Research funding from Boehringer Ingelheim, Chugai Pharma, MSD Oncology, Sanofi-Aventis, Taiho Pharmaceutical, Takeda, and Yakult Honsha. S. Nomura: An immediate family member has been employed by Asahi-Kasei pharma. K. Shitara: Receipt of grant/research supports from Daiichi Sankyo, Chugai Pharma, Lilly, MSD, Taiho Pharmaceutical and Dainippon Sumitomo Pharma. A. Ohtsu: An immediate family member has been employed from Celgene. Research Funding from Bristol-Myers Squibb. T. Yoshino: Research funding from GlaxoSmithKline K.K. and Boehringer Ingelheim GmbH. All other authors have declared no conflicts of interest.