The Study: This analysis of The Cancer Genome Atlas (TCGA) reveals a new surrogate for tumor mutational burden in gastric cancer. In other words, they found something besides MSI that can be used to indicate stronger tumor immunogenicity. This, in turn, typically translates to a better natural history from native immunity as well as more robust responses to immunotherapy. Among 467 gastric cancer samples from TCGA, over one-third contained mutations in MUC16, a gene encoding CA-125. This was subsequently validated with 256 samples from an Asian cohort where nearly a quarter harbored MUC16 mutations. In both cohorts, samples with MUC16 mutations had roughly twice the median number of mutations per megabase. Not surprising, then, was that immune response was a top altered signaling pathway seen with this mutation. Nor that the median overall survival was more than 20 months longer among those with MUC16 mutations than those without.
Bottom Line: Stay tuned because MUC16 mutations may be the newest way to select which patients with gastric cancer will benefit from upfront immune checkpoint inhibition. | Li, JAMA Oncol 2018