The Landscape and Prognosis of Microsatellite Stable (MSS) Esophageal, Gastro-Esophageal Junction and Gastric Adenocarcinomas with High Tumor Mutation Burden (TMB).

BACKGROUND

A minority of patients with MSS tumors present a high tumor mutation burden (TMB) without underlying MMR defects.

METHODS

Publicly available genomic series were assessed for identification of patients with MSS gastric gastroesophageal junction, and esophageal adenocarcinomas and a high TMB, defined as more than 10 mutations per Mb. These were compared with MSS cancers and a low TMB for genetic alterations and for survival outcomes.

RESULTS

Patients with MSS cancers with high TMB in the MSK series were older but did not differ in other clinicopathologic parameters compared with MSS patients with low TMB. Mutations in tumor suppressors and and oncogenes and as well as amplifications of were more prevalent in the high TMB group of MSS cancers. Mutations in DDR associated genes, in epigenetic modifiers and in genes associated with immune response were more prevalent in the hIgh TMB group patients. However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank  = 0.5).

CONCLUSION

MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways.