635P - Genetic analysis of gastric cancer with distinctive family history

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Gastric Cancer
Presenter Masanori Terashima
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors M. Terashima1, K. Hatakeyama2, M. Kusuhara3, R. Makuuchi1, M. Tokunaga1, Y. Tanizawa1, E. Bando1, T. Kawamura1, M. Hikage1, S. Kaji1, K. Ohshima4, S. Ohnami5, K. Urakami5, K. Yamaguchi6
  • 1Division Of Gastric Surgery, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 2Medical Genetics, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 3Region Resources, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 4Medical Genetics, Shizuoka Cancer Center, Shizuoka/JP
  • 5Cancer Diagnostic Research, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 6Research Institution, Shizuoka Cancer Center, 4110942 - Shizuoka/JP

Abstract

Background

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant susceptibility for diffuse gastric cancer. Germ line mutation of CDH1 is observed in 30-50% of the HDGC, however, disease susceptibility genes have not yet identified in remaining 50-70%. Project HOPE is a comprehensive genetic analysis project including whole exome sequencing and gene expression analysis using fresh frozen samples obtained from various patients undergoing surgery in Shizuoka Cancer center. In order to evaluate the genetic alterations in diffuse gastric cancer with family history, genetic analysis results were compared between patients with and without family history.

Methods

Out of 188 patients registered in HOPE project, 51 patients with diffuse gastric cancer were included. In these patients, results from exome sequencing and gene expression analysis were compared between patients with family history (FDGC) and those without family history (NFDGC). Family history was defined as the presence of two or more documented cases of diffuse gastric cancer in first- or second-degree relatives OR solitary diffuse gastric cancer diagnosed prior to age 40years. Whole exome sequencing was performed using Ion Proton to identify tumor specific gene mutations and to estimate the copy number with lymphocytes as normal control. Gene expression analysis was performed using DNA Microarray with adjacent normal tissue as a control.

Results

Three patients were classified to FDGC and 48 were to NFDGC. FDGC were tended to be younger, predominantly female and more advanced stage than NFDGC. Germline mutation of CDH1 was not observed. Diffuse gastric cancer were separated into two groups, 27 patients with FDGC and 24 patients without FDGC, by gene expression profiling. In patients including FDGC, gene expression of PPP1R14C, ABCG5, NR1I2, APOC2, MLK7-AS1 and PRB2 were observed. In somatic mutation analyses, the incidence of RHOA and CDH1 mutations was higher in patients with FDGC (19% vs 4%, 22% vs 13%). CDH1 mutation was observed in 2 of 3 FDGC.

Conclusions

Gene cluster that was highly expressed in FDGC was identified. Diffuse gastric cancer was classified into two groups by cluster analysis with these genes. Somatic mutation of CDH1 was frequently observed in patients group with FDGC.

Clinical trial identification

Legal entity responsible for the study

Shizuoka Cancer Center

Funding

Shizuoka Cancer Center

Disclosure

All authors have declared no conflicts of interest.