716P - The nationwide cancer genome screening project in Japan, SCRUM-Japan GI-screen: Efficient identification of cancer genome alterations in advanced biliary tract cancer

Abstract

Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in cancers of digestive system, called as the SCRUM-Japan GI-SCREEN. We evaluated the frequency of cancer genome alterations. We show the result of advanced biliary tract cancer cohort (aBC; intra hepatic bile duct (IHBD), extrahepatic bile duct (EHBD), gallbladder (GB), and ampulla of Vater (AV)). Methods: This study is ongoing with the participation of 20 major cancer centers. Patients who plan to or receive systemic 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 mutation, copy number variant (CNV) and 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. Results: As of October 31st in 2016, a total of 108 aBC samples were analyzed and the sequence with the OCP was successfully performed in 73 (67.6%). The frequent/important mutations in 73 samples of which results were available were shown in table. The druggable CNVs (≥ 7 copies) were CDK4/6 (n = 4), EGFR (2), FGFR3 (2), and ERBB2 (1). No gene fusion was detected. Proportion of gene mutations: n (%)Table716PIHBD n = 31EHBD n = 27GB n = 10AV n = 5KRAS10(32)8(26)2(20)2(40)TP535(16)6(19)6(60)2(40)BRAF01(3)01(20)PIK3CA004(40)0BRCA202(6)00ATM1(3)2(6)1(10)0IDH13(10)1(3)00FGFR2/32(6)001(20)ERBB31(3)3(10)00 Open table in a new tab Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aBC. 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 15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC. Disclosure: M. Ueno: Honoraria: Taiho Pharmaceutical, Yakult Honsha, Ono Pharmaceutical, AstraZeneca, Novartis, and Lilly. Research funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, and NanoCarrier. C. Morizane: Advisort role: AstraZeneca, Novartis. Honoraria: Pfizer, Novartis, Yakult Honsha, Nobelpharma, Fujifilm. Research funding: GlaxoSmithKline, Pfizer, Nobelpharma, Eisai, Ono Pharmaceutical, Taiho Pharmaceutical. Y. Kawamoto: Honoraria: Sawai Pharmaceutical Co, Taiho Pharmaceutical. H. Takahashi: Travel: Pfizer Honoraria: Taiho Pharmaceutical Research Funding: Bayer, Bristol-Myers Squibb. D. Naruge: Research funding: Ono Pharmaceutical, Merck Serono, Lilly Japan, Takeda, Takeda, Chugai Pharma, Bayer, GlaxoSmithKline, Yakult, Sumitomo Dainippon, etc. S. Shimizu: Honoraria: Taiho Pharmaceutical, Nihonkayaku, Novartis. T.E. Nakajima: Honoraria: Lilly Japan, Kyowa Hakko Kirin, Hisamitsu Pharmaceutical, Merck Serono, Takeda, Bristol-Myers Squibb, Ono Pharmaceutical, Dainippon Sumitomo Pharma, Taiho Pharmaceutical, etc. Research funding: Lilly Japan, Chugai Pharma, etc. T. Kato: Speakers' Bureau: Chugai Pharma, Takeda, Lilly, Yakult. T. Kudo: Honoraria: Chugai Pharma, Merck Serono, Takeda, Lilly, Bayer, Taiho Pharmaceutical. Research Funding: Chugai Pharma, Yakult Honsha, Ono Pharmaceutical, Lilly. N. Mizuno: Speakers' Bureau: Taiho Pharmaceutical Travel: Novartis, etc. Honoraria: Taiho Pharmaceutical, Yakult Honsha, Novartis, etc. Research Funding: Taiho Pharmaceutical, Merck Serono, AstraZeneca, etc. H. Ishii: Advisory Role: Ono Pharmaceutical Honoraria: Yakult Honsha, Taiho Pharmaceutical, Lilly Japan, Kyowa Hakko Kirin, Nobelpharma, Mochida Pharmaceutical Co. Ltd, Hospira. Research Funding: Taiho Pharmaceutical. S. Nomura: Employment: Asahi Kasei An Immediate Family Member. K. Shitara: Advisory Role: Chugai Pharma, Takeda, Bayer, Lilly. Honoraria: Bristol-Myers Squibb, Novartis, etc. Research Funding: Dainippon Sumitomo Pharma, MSD, Sanofi, Daiichi Sankyo, Taiho Pharmaceutical, etc. A. Ohtsu: Employment: Celgene An Immediate Family Member Research Funding: Bristol-Myers Squibb. T. Yoshino: Research Funding: GlaxoSmithKline, K.K.Boehringer Ingelheim GmbH. All other authors have declared no conflicts of interest.