The nationwide cancer genome screening project in Japan, SCRUM Japan GISCREEN: Efficient identification of cancer genome alterations in advanced biliary tract cancer.
ANNALS OF ONCOLOGY(2018)
Abstract
Background: We initiated the Nationwide Cancer Genome Screening Project in Japan since February 2014. From October 2015, we have introduced the Next Generation Sequencing to detect cancer genome alterations in advanced biliary tract cancer (aBTC; intrahepatic bile duct, extrahepatic bile duct, gallbladder, and ampulla of Vater), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations and to identify patients who are candidate for clinical trial with corresponding targeting agents. Methods: This study is ongoing with 20 major cancer centers. Patients with aBTC who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from formalin-fixed paraffin embedded tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect mutations, copy number variant (CNV) and fusion genes in a CLIA certified CAP accredited lab. 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 March 31st 2017, a total of 167 aBTC patients were enrolled and 140 samples were analyzed. The sequence was successfully performed in 92 tumors (65.7%). The frequently detected gene alterations were shown in table. No gene fusion was detected. We will show the clinical outcome based on certain key cancer genome alterations.Table: 623PDIHBD n = 36EHBD 35GB 14VP 7n(%)TP53 mutation(m)9(25)11(31)8(57)4(57)KRAS m12(33)11(31)2(14)4(57)IDH1 m5(14)1(3)00ERBB3 m1(3)3(9)1(7)0ERBB2 m CNV ( > 7copies)0 02(6) 1(3)1(7) 1(7)0 0CTNNB1 m1(3)1(3)1(7)2(29)PIK3CA m004(29)1(14)CDKN2A m3(8)02(14)0APC m2(6)1(3)01(14)ATM m1(3)2(6)1(7)0FGFR3 m CNV1(3) 00 2(6)0 1(7)0 0MDM2 CNV1(3)1(3)1(7)1(14)SMAD4 m2(6)1(3)01(14)STK11 m02(6)1(7)1(14)TET2 m01(3)2(14)1(14)CCNE1 m1(3)03(21)0 Open table in a new tab Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aBTC. This novel knowledge provides an intriguing background to investigate new targeted approaches in these patients and to progress precision medicine. Clinical trial identification: UMIN000016344. Date of disclosure of the study information2015/01/26. Legal entity responsible for the study: SCRUM-Japan. Funding: 15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC. Disclosure: C. Morizane: Honoraria: Pfizer, Novartis, Yakult Honsha, Lilly, Nobelpharma, Fujifilm, Teijin Pharma, Taiho Pharmaceutical; Consulting or advisory role: Yakult Honsha, Novartis, Taiho Pharmaceutical; Research funding (to institution): Pfizer, Nobelpharma, Eisai, Yakult Honsha, Ono Pharmaceutical, Taiho Pharmaceutical. Y. Komatsu: Honoraria: Pfizer, Novartis, Bayer,Yakult Honsha, Lilly, Merck, Taiho, Takeda, Sanofi, Chugai, Ono, Asahi-kasei, Kirin-Kyowa, Nipro, Towa. H. Takahashi: Honoraria: Taiho Pharmaceutical; Research funding: Bayer Pharmaceutical, Bristol-Myers Squibb. M. Ueno: Honoraria: Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Novartis, Lilly, Teijin Pharma, Shire, Ono Pharmaceutical; Research funding: Taiho Pharmaceutical, Shire, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Serono, NanoCarrier, Dainippon Sumitomo Pharma, Incyte. J. Furuse: Honoraria: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Mochida, Nippon Kayaku, EA pharma, Sawai, Teijin Pharma; Consulting or advisory role: Taiho, Chugai, Yakult, Sumitomo Dainippon, Eli Lilly Japan, Astellas, Ono, Pfizer, Bayer, Novartis, Merck Serono, Takeda, Eisai, MSD, Shionogi, J-Pharma, Daiichi Sankyo, Kyowa Hakko Kirin, Sanofy, Sandoz, Otsuka, Zeria, Fujifilm, AstraZeneca, Asahi Kasei, Shire; Research funding (to institution): J-Pharma, Taiho, Sumitomo Dainippon, Janssen, Daiichi Sankyo, MSD, Yakult, Takeda, Chugai, Ono, Astellas, Zeria, Novartis, Nanocarrier, Shionogi, Onco Therapy Science, Eli Lilly Japan, Bayer, Bristol-Myers Squibb, Merck Serono, Kyowa Hakko Kirin, Eisai, NanoCarrier, Mochida, Baxalta, Sanofi. T. Kudo: Research grants: Yakult Honsha, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. S. Itoh: Speakers' bureau: Otsuka Pharmaceutical, Asahi Kasei Phama; Consulting or advisory role: Asahi Kasei Phama, Takeda; Research funding (to institution): Taiho, Sumitomo Dainippon, Daiichi Sankyo, MSD, Yakult, Chugai, Ono, Astellas, CSL Behring, Novartis, Shionogi, Eli Lilly Japan, Bayer, Merck Serono, Kyowa Hakko Kirin, Sanofy, Pfizer, Boehringer Ingelheim, Asahi Kasei Phama, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Hisamitsu Pharmaceutical, Nihon Pharmaceutical, Nihon Blood Products Organization, Kowa Company, Medtronic, Johnson and Johnson. S. Shimizu: Honoraria: Novartis, Taiho Pharmaceutical. T. Mizukami: Speakers' bureau: Taiho Pharma, Teijin Pharm. Inc., Otsuka Pharmaceutical Co., Ltd. Consulting or Advisory role: Merck Serono. S. Nomura: Honoraria: Taiho Pharmaceutical. T. Kuwata: Honoraria: Chugai Pharm, Daiichi-Sankyo; Research Funding (to institution): Daiichi-Sankyo. W. Okamoto: Grants: MSD, outside the submitted work. K. Shitara: Consulting or advisory role: Astellas Pharma, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono Pharmaceutical; Personal fees: Novartis, AbbVie, Yakult; Research funding (to institution): Lilly, Ono Pharmaceutical, Dainippon Sumoitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharma, MSD. A. Ohtsu: Honoraria: Chugai, Ono Pharmaceuticals, BMS; Research Funding: BMS. T. Yoshino: Grants: MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., GlaxoSmithKline K.K., Nippon Boehringer Ingelheim Co., Ltd.; Grants and personal fees: Sanofi K.K., Chugai Pharmaceutical Co., Ltd, Personal fees: Eli Lilly Japan K.K, Merck Serono Co., Ltd., outside the submitted work. All other authors have declared no conflicts of interest.
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Key words
Biliary Tract Cancer,Cancer Genomics
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