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. In this presentation, we show the result of advanced pancreatic cancer (aPC).
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. In this presentation, we show the results of aPC cohort.
As of 31st October 2016, a total of 179 aPC samples were analyzed. The sequence with the OCP was successfully performed in 120 (67.0%). Out of 120 patients, the proportion of location of tumor and histology type is follows; Ph = 44%, adenocarcinoma 97%. The proportion of procedure for sample collection is follows; surgical resection 35.0%, needle biopsy 38.3%, EUS-FNA 20.0%, other 5.8%, and unknown 0.8%.The frequently detected mutations (> 10%) in 120 samples of which results were available were KRAS (93%), TP53 (63%), CDKN2A (12%), and SMAD4 (11%). Other important/druggable mutations were GNAS, BRCA2, and ATM (3%, each). Most frequently detected CNVs (≥ 7copies) was MYC (3%), and no gene fusion was detected.
This nationwide screening system is efficient to detect rare gene alterations in aPC. Alterations in potentially druggable genes were limited in aPC, but homologous recombination repair genes were attractive target. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine.
Clinical trial identification
Clinical trial information: UMIN000016344
Legal entity responsible for the study
15 SCRUM-Japan collaborating pharmaceutical companies, AMED, NCC
D. Naruge: Research Funding in institution: Taiho, Ono Pharmaceutical, Merck Serono, Takeda, Lilly Japan, Chugai Pharma, Bayer, GlaxoSmithKline, Yakult, Novartis, J-Pharma, Janssen, Sanofi, Kyowa Hakko Kirin, Daiichi Sankyo, Astellas, Pfizer, etc. C. Morizane: Consulting Role: AstraZeneca, Yakult, Novartis, Taiho Pharmaceutical. Honoraria: Pfizer, Novartis, Yakult, Lilly, Nobelpharma, Fujifilm. Research Funding: GlaxoSmithKline, Pfizer, Nobelpharma, Eisai, Yakult, ONO PHARMACEUTICAL, Taiho Pharmaceutical. M. Ueno: Consulting Role: Eisai. Honoraria: Taiho, Yakult, Ono Pharmaceutical, AstraZeneca, Novartis, Lilly. Research Funding of your institution: Taiho Pharmaceutical, Daiichi Sankyo, Eisai, AstraZeneca, Merck Serono, Ono Pharmaceutical, MSD. H. Takahashi: Honoraria: Taiho Pharmaceutical. Research Funding of your institution: Bayer, Bristol-Myers Squibb. Travel, Accommodations, Expenses: Pfizer. Y. Kawamoto: Honoraria: Sawai Pharmaceutical Co. S. Shimizu: Honoraria: Taiho Pharmaceutical, Nihonkayaku, Novartis. T.E. Nakajima: Honoraria: Taiho, Lilly, Chugai, Kyowa Hakko Kirin, Merck Serono, Takeda, Ono. Research Funding: Taiho, Ono, AstraZeneca, Lilly, Chugai, Kyowa Hakko Kirin, Merck Serono, Takeda, MSD, Eisai, Amgen Asetlas Biopharma K.K., Eisai Pharm, etc. H. Ishii: Advisory Role: Ono Pharmaceutical. Honoraria: Yakult, Taiho, Lilly Japan, Kyowa Hakko Kirin, Nobelpharma, Mochida Pharmaceutical Co. Ltd., Hospira. Research Funding: Taiho Pharmaceutical. T. Kato: Speakers\' Bureau: Chugai Pharma, Takeda, Lilly, Yakult. T. Kudo: Research Funding: Yakult, Chugai Pharma, Ono Pharmaceutical. S. Nomura: Employment: An Immediate Family Member is employed by Asahi-Kasei Pharma. K. Shitara: Research Funding: Daiichi Sankyo, Chugai Pharma, Lilly, MSD, Taiho Pharmaceutical, Dainippon Sumitomo Pharma. A. Ohtsu: Employment: An Immediate Family Member is employed by Celgene. Research Funding: Bristol-Myers Squibb. T. Yoshino: Research funding: GlaxoSmithKline K.K., Boehringer Ingelheim GmbH. All other authors have declared no conflicts of interest.