Abstract 2712: Relationship between CLDN18-ARHGAP fusion gene and clinicopathological features of gastric cancer in young adult
Authors: Nakayama Izuma , Shinozaki Eiji , Sakata Seiji , Yamamoto Noriko , Baba Satoko , Yamaguchi Kensei , Takahashi Shunji , Takeuchi Kengo , Noda Tetsuo 
Published: July 2017

Introduction: Gastric cancer (GC) in young adults comprises a small part of this disease population having the distinctive clinicopathological features, such as diffusive tumor growth and peritoneal dissemination. Genetic alterations underlying these features and the development of cancer in early ages remain unclear. Comprehensive molecular analyses by TCGA have suggested 4 molecular subtyping of GC and revealed enrichment of CLDN18-ARHGAP fusion gene in Genomically stable (GS) type which mainly included diffuse type. In this study, we examined the relationship between CLDN18-ARHGAP and clinicopathological features of GC affecting young adults.

Method: Patients (pts) diagnosed at the age younger than 40 years-old were defined as the GC in young adults, and underwent surgery at our institute between Jan 2006 and Dec 2015 were enrolled to this study. Tissue microarrays were prepared from formalin-fixed and paraffin-embedded surgical specimen. DNA probes for CLDN18, ARHGAP-26 and -6 were created using bacterial artificial chromosomes and fusion genes were detected by a FISH method.

Results: Out of 155 surgical specimens available for analysis, we found CLDN18-ARHGAP fusion gene in 21 pts (13.5%). Among these, 19 cases were CLDN18-ARHGAP26 fusion and the others were CLDN18-ARHGAP6. Cancers with CLDN18-ARHGAP fusion genes were all diagnosed as diffuse type and included more large-sized, multiple lymph node metastases and advanced stages tumors (table 1). The proportion of detected fusion genes in this study was almost equivalent to that of GS type in TCGA cohort. Analysis of variations of breakpoint is planned to confirm by RT-PCR and sequencing. Additionally, we are going to study the association of CLDN18-ARHGAP with RHOA or CDH-1.

Conclusion: CLDN18-ARHGAP fusion gene might account for the characteristic of a part of diffuse type GC. Further comprehensive molecular analysis comparing to general GC population is warranted.

Patient demographicspositive (n=21)negative (n=134)p-valueAge0.646&lt;30 / 30-392 / 199 / 125Sex0.482man / woman8 / 1365 / 69Tumor location0.507Upper /Middle /Lower4 / 10 / 743/ 53 / 38Tumor size (mm)75.664.70.117≤80 / 80&lt;9 / 1234 / 100Borrmann0.648Type2 / 3 / 4 / others0 / 8 / 3 / 1010 / 38 / 20 / 62LaurenNSintestinal / diffuse / mixed0 / 21 / 05 / 124 / 5T (TNM)0.479T1 / T2 / T3 / T46 / 1 / 4 / 1050 / 18 / 18 / 48N (TNM)0.044N1 / N2 / N36 / 2 / 2 / 1171 / 12 / 20 / 31Stage (TNM)0.032I / 2 / 3 / 47 / 1 / 5 / 857 / 28 / 31 / 18

Citation Format: Izuma Nakayama, Eiji Shinozaki, Seiji Sakata, Noriko Yamamoto, Satoko Baba, Kensei Yamaguchi, Shunji Takahashi, Kengo Takeuchi, Tetsuo Noda. Relationship between CLDN18-ARHGAP fusion gene and clinicopathological features of gastric cancer in young adult [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2712. doi:10.1158/1538-7445.AM2017-2712