Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan
Satoshi Yuki , Kohei Shitara , Shigenori Kadowaki , Keiko Minashi , Atsushi Takeno , Hiroki Hara , Takeshi Kajiwara , Yu Sunakawa , Satoru Iwasa , Yoshiyuki Yamamoto , Fumio Nagashima , Ryota Nakanishi , Taito Esaki , Takaki Yoshikawa , Shogo Nomura , Takeshi Kuwata , Satoshi Fujii , Wataru Okamoto , Atsushi Ohtsu , Takayuki Yoshino
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: Patients with aNon-CRC, 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 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 whether 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 gastric cancer (aGC) cohort. Results: From April 2015 to March 2017, a total of 696 aGC samples from 20 cancer centers were analyzed. The sequence with the OCP was successfully performed in 513 (73.7%). The frequently detected mutations were TP53 (47.8%), PIK3CA (9.2%), KRAS (6.0%), SMAD4 (5.1%), APC (4.1%), TET2 (3.9%), ERBB2 (3.3%) and CNVs were ERBB2 (11.3%), CCNE1 (11.1%), KRAS (3.7%), FGFR2 (3.3%), ZNF217 (3.3%), MYC (2.7%), CCND1 (2.3%) and CDK6 (2.1%). FGFR3-TACC3 fusion, EGFR vIII, WIPF2-ERBB2 fusion, and GOPC-ROS1 fusion were detected in 2, 2, 1, and 1 cases, respectively. Seven patients with druggable genomic alterations were enrolled for clinical trials of targeting therapies. We will show the clinical outcome based on certain key cancer genome alterations. Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aGC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. This study is still ongoing with newer panel as Oncomine Comprehensive Assay version 3. Clinical trial information: UMIN000016344.
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Abstract Disclosures
2017 ASCO Annual Meeting
First Author: Shigenori Kadowaki
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First Author: Brendon Fusco
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