Abstract 140P
Background
Nowadays, the prognosis of gastric cancer remains unsatisfactory, and the efficacy of ICIs in its treatment has been confirmed by clinical trials. Tumor mutation burden (TMB) and microsatellite instability (MSI) status have been confirmed to be promising predictive biomarkers of ICIs in gastric cancer. However, the relation between these prognostic markers and mutation genes has not been investigated. KMT2C/D, which encode histone H3 lysine 4 methyl-transferases, are frequently mutated in gastric cancer; while, their association with immunotherapy remains unclear. In this study, we explored the correlation between KMT2C/D genetic status and immunotherapy prognostic biomarkers in gastric cancer.
Methods
Whole-exome sequencing data of 295 gastric cancers from The Cancer Genome Atlas (TCGA) were retrospectively analyzed. TMB was defined as total number of somatic non-synonymous mutations per coding region of tumor genome. The fraction of copy number altered genome (FGA) was defined as the fraction of genome with log2 copy number gain > 0.2 or loss <-0.2 relative to the size of the genome with copy number profiled.
Results
Two patients were excluded by lack of clinical information. Totally 22.18% (65/293) of gastric cancers in TCGA clinical cohort harbored KMT2C/D mutation (KMT2C was 11.26%, and KMT2D 17.06%). The frequency of MSI-H was significantly higher in KMT2C/D mut group (52/65, 80%) than in KMT2C/D non-mut group (11/228, 4.82%; p<0.0001). In addition, KMT2C/D mutation was significantly associated with higher TMB (median, 29.9 vs 2.99; p<0.0001). Furthermore, previous studies have shown that copy-number alteration correlates with worse survival in immunotherapy, which means that FGA is a poor prognostic biomarker of immunotherapy. Gastric cancers with KMT2C/D exhibited significantly lower FGA than those without KMT2C/D mutations (median FGA: 0.085 with KMT2C/D vs 0.20805 without, p<0.0001).
Conclusions
These results show that KMT2C/D mutations may be associated with higher TMB, MSI and lower FGA in gastric cancer. KMT2C/D genes might serve as promising prognostic factors for its immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.