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. The objective is to evaluate the frequency of cancer genome alterations in aNon-CRC and to identify patients who are candidate for clinical trial for corresponding targeting agents. Methods: This study is ongoing with the participation of 20 major cancer centers. Patients with aNon-CRC, including advanced esophageal cancer (aEC), 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 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 aEC cohort. Results: As of October 31^st in 2016, a total of 180 aEC samples were analyzed. The sequence with the OCP was successfully performed in 121 (67.2%). Out of 157 patients except for the 23 patients in which precise data is not collected, the proportion of sample and histology type is followed; surgical specimen 58.0%, squamous cell carcinoma 92.4%. The frequently detected mutations in 114 samples of which results were available were TP53 (77.2%), NFE2L2 (23.7%), CDKN2A (9.6%), PIK3CA (7.0%), RB1 (6.1%), and CNVs were CCND1 (37.7%), EGFR (7.9%), MYC (7.9%), SOX2 (6.1%), ATP11B (5.3%), NKX2-1 (5.3%). ERBB2 amplification was identified in 3 cases (2.6%) and FGFR3-TACC3fusion was identified in one case (0.9%). Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aEC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.