Comprehensive genomic profiling of gastric cancer to reveal distinctive genomic alterations between peritoneal metastasis (PM) patients (pts) and non-PM pts.

Author:Rongbo Lin, Xianchao Guo, Ying Chen, Hui Li, Jie Liu, Shen Zhao, Jiaqing Yu, Nanfeng Fan

Background: PM is the main cause of death in gastric cancer. PM of gastric cancer is difficult to diagnose in its early stage due to lack of obvious clinical signs and symptoms. Comprehensive genome analysis of the primary tumor provides a new strategy for uncovering the pathogenesis and molecular diagnosis of PM. 

Methods: DNA was extracted from FFPE samples of the primary tumors from 10 pts with PM and 9 pts without PM (non-PM). Comprehensive genomic profiling was performed using a 1.24M size panel covering exon regions of 1,346 genes based next generation sequencing assay. Somatic Mutations were analyzed to investigate the difference of molecular features between the gastric pts with or without PM. 

Results: The most frequently mutated genes were TP53, RAD50, ZFHX4. In addition, frequent mutations in chromatin remodeling genes such as KDM5A, KMT2C, KAT6A and HDAC2 were detected. Mutations ofGPI, JAK3, PRSS8 and IDH3G are more common in non-PM pts than in PM pts (p < 0.05). Four mutations (PRDM1, c.950G > A; XPC, c.1315G > C; CD68, c.554A > C; ACVR1B, c.1345C > A) were only identified in PM pts. 

Conclusions: Comprehensive genomic profiling of gastric cancer reveals distinctive genomic alterations between PM pts and non-PM pts. Several possible candidate genes that may be helpful for PM of gastric cancer were identified in this small cohort. Expanded prospective cohorts are warranted to further elucidate these findings.