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Genetic analysis of gastric cancer with distinctive family history

Date

08 Oct 2016

Session

Poster Display

Presenters

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

Author affiliations

  • 1 Division Of Gastric Surgery, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 2 Medical Genetics, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 3 Region Resources, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 4 Medical Genetics, Shizuoka Cancer Center, Shizuoka/JP
  • 5 Cancer Diagnostic Research, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
  • 6 Research Institution, Shizuoka Cancer Center, 4110942 - Shizuoka/JP
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Resources

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.

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