MUC16 Mutation, Tumor Mutation Load, and Prognosis in Gastric Cancer
In a study reported in JAMA Oncology, Li et al found that MUC16 mutation was associated with increased tumor mutation load and improved prognosis in gastric cancer.
The study involved analysis of genomic data from 437 gastric cancer samples from The Cancer Genome Atlas (TCGA; discovery set) and 256 samples from an Asian cohort (validation set). MUC16 mutation was found in 168 TCGA samples (38.4%) and 57 Asian cohort samples (22.3%).
Tumor Mutation Load and Prognosis
Samples with MUC16 mutations had significantly greater tumor mutation load in both the TCGA cohort (median mutation counts = 264 with mutation vs 115 without, P <.001) and the Asian cohort (134 with mutation vs 74 without, P < .001). The association was independent of POLE and BRCA1/2 mutations and mutational signatures in the TCGA cohort (odds ratio [OR] = 1.87, P < .001) and Asian cohort (OR = 1.69, P < .001).
Patients with MUC16 mutation had significantly better median overall survival in both the TCGA cohort (46.9 vs 26.7 months, P = .007) and the Asian cohort (not reached vs 36.8 months, P = .04). Analysis in the Asian cohort showed that the association remained significant after controlling for age, sex, TNM stage, mutations in POLE and BRCA1/2, and mutational signatures (hazard ratio = 0.61, P = .01). Immune response and cell-cycle regulation circuits were among the most frequently altered signaling pathways in samples with MUC16 mutation.
The investigators concluded, “These findings indicate that MUC16 mutations may be associated with higher [tumor mutation load], better survival outcomes, and immune response and cell cycle pathways. These findings may be immediately applicable for guiding immunotherapy treatment for patients with [gastric cancer].”
The study was supported in part by grants from the Program for Changjiang Scholars and Innovative Research Team in University in China and the U.S. National Cancer Institute.
Kexin Chen, MD, PhD, of the Tianjin Medical University Cancer Institute and Hospital, and Wei Zhang, PhD, of Wake Forest Baptist Comprehensive Cancer Center, are the corresponding authors for the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
