Identification of molecular alteraction in gastric neuroendocrine carcinoma

Research Project

Project/Area Number	15K19318
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	University of Toyama
Principal Investigator	Ando Takayuki 富山大学, 附属病院, 講師 (30600671)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	胃神経内分泌がん / DNAメチル化 / 血管新生 / 胃神経内分泌癌 / メチル化 / VEGFR2
Outline of Final Research Achievements	Neuroendocrine cancer (NEC) of the stomach is a rare type of cancer, and its molecular characterization is poorly understood. Therefore, we aimed to find NEC-specific alterations in comparison with adenocarcinoma. Analysis of DNA methylation was performed using the Infinium HumanMethylation 450 BeadChip array, and sequence variations of 55 cancer-related genes was performed using the Ion AmpliSeq Panel Kit. Comprehensive methylation analysis of 20 gastric cancers revealed that the number of aberrantly methylated genes was highly variable between individual gastric NEC and adenocarcinoma. Among the hundreds of tumor-specific methylations discovered, 13 genes (RPL37, ZNF175, SLC7A5P1, HAPLN3, GNG7, CCDC126, ZFP3, EIF2C1, HFN1B, ZNF665, TLE1, TMCO1, TMPRSS2) with promoter methylation were identified. Additionally, VEGFR2, which is controlled by one of identified genes, was highly expressed in gastric NEC. Indeed, paclitaxel and ramucirumab treatment was effective for advanced gastric NEC.