175P - Genomic evolution of peritoneal metastasis in gastric adenocarcinoma

Background

Advanced gastric adenocarcinoma with both lymph node and peritoneal metastasis has notoriously poor prognosis. However, molecular mechanism of the metastatic process and potential therapeutic targets remain unknown, hence limiting the development of new therapies.

Methods

We recruited 13 treatment-naïve patients who had gastric adenocarcinoma with concurrent lymph node and peritoneal metastasis. DNA and RNA were extracted from tumor biopsy samples collected from the stomach, lymph node and peritoneum, together with 2 mL of peripheral blood for each patient. Whole exome sequencing (WES) and transcriptome sequencing were performed to generate a comprehensive genomic dataset of our cohort.

Results

Analysis of WES data showed that TP53 and CDH1 were the most frequently mutated genes in both the primary and metastatic tumors. All patients had low tumor mutational burden, but 31% (n=4) showed high level of chromosomal instability (CIN). By constructing tumor phylogenetic trees for each patient, we found evidence supporting two distinct processes of peritoneal dissemination that involved either lymphatic system (n=5) or direct seeding into the peritoneal cavity (n=4). In the RNA sequencing analysis, epithelial-mesenchymal transition (EMT) pathway was found the most significantly altered and segregated the patients into the EMT-high group (n=10) that upregated genes in the EMT pathway, and the non-EMT-high group (n=3).

Conclusions

Multi-omics profiling in this study revealed mutational signature and altered signaling pathways in lymph node and peritoneal metastasis. The results could help identify distinct molecular subtypes among patients, laying foundation for the development of molecular-guided therapeutic strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Medical Genetics Institute, Ho Chi Minh city, Vietna.

Funding

Gene Solutions JSC, Ho Chi Minh city, Vietnam.

Disclosure

All authors have declared no conflicts of interest.