Genetic mutations in recurrent and/or metastatic nasopharyngeal carcinoma – an analysis of the Japanese national genomic profiling database

Introduction: Although genetic mutations have been reported in nasopharyngeal carcinoma (NPC), there are currently no scientifically validated treatments targeting these mutations. Furthermore, cancer genomic profiling tests are underutilized in clinical practice. This highlights an urgent need to explore the genomic landscape of NPC and its potential therapeutic implications.Aim: The aim of this study is to investigate the genetic mutational landscape of recurrent and/or metastatic nasopharyngeal carcinoma (NPC).Materials and methods: Data were analyzed for 67 consecutive patients with NPC registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and May 2024. Genetic mutations were determined by FoundationOne CDx or Liquid CDx next-generation sequencing. Survival of patients was determined by the log-rank test and a Cox proportional hazards model.Results: The top 10 mutations in NPC were CDKN2A (41.8%), CDKN2B (31.3%), TP53 (20.9%), KMT2D (20.9%), DNMT3A (19.4%), NOTCH1 (17.9%), STK11 (17.9%), MTAP (17.9%), EP300 (17.9%), TSC1 (13.4%), with 11.1 6.1 (mean SEM) mutations/individual. Mutations in KMT2D (p = 0.0127), DNMT3A (p = 1.41×10-7), GNAS (p = 3.64×10-11), SPEN (p = 0.0167), BRCA1 (p = 0.0379), and KMT2A (p = 2.06×10-5) were associated with a significantly worse prognosis, as determined by the log-rank test. The hazard ratios for cases with these mutations were 0.0122 (95% CI, 1.58×10-4-0.936, p = 0.046) for TP53, 1847.0 (95% CI, 4.619-7.386×105, p = 0.014) for DNMT3A, 126.7 (95% CI, 1.262-12720, p = 0.039) for BRCA2, 197.9 (95% CI, 2.844-13770, p = 0.015) for ALK, 34.22 (95% CI, 1.256-932.7, p = 0.036) for SPEN, and 6.445×10-4 (95% CI, 2.913×10-6-0.143, p = 7.6×10-3) for MYCL.Conclusions: This study identified genetic mutations in recurrent and/or metastatic NPC. Even in advanced cases, prognosis-related mutations were identified, underscoring the importance of cancer genomic profiling tests.