Abstract 942P
Background
Despite most nasopharyngeal carcinoma (NPC) patients demonstrate favorable outcomes after initial radiotherapy and/or chemotherapy, some patients experience recurrence at a later date. However, the genomic alterations associated with the development of recurrence is unclear.
Methods
This study investigated the genomic alterations by comprehensive genomic profiling using deep targeted next-generation sequencing in 30 tumor tissue samples of 22 NPC cases (15 patients without relapse and 7 patients with relapse), including 15 pre-treatment primary tumors of patients without relapse, 7 pre-treatment primary tumors and 8 post-treatment recurrent tumors (one patient has two subsequent recurrent tumors) of patients with relapse.
Results
Kaplan-Meier and Cox regression analysis revealed that the genomic alterations of 5 genes (TP53, VEGFB, CDKN1B, PRDM1 and MEN1) were significantly associated with a shorter overall survival of these 22 patients (p < 0.03). These 5 genes were also significantly (p < 0.03) altered comparing the primary tumors of patients with (n = 7) and without relapse (n = 15). On the other hand, MUC16 mutation was prominently detected (73.3%) in all the 30 tumor tissues, while the amplifications of PRDM1, PSMB8, PSMB9, TAP1 and TAPBP were only found (57.1%) in the primary tumors (n = 7) of patients with relapse. CDK2 and ERBB3 amplifications were only detected (37.5%) in the recurrent tumors (n = 8) of patients with relapse but not in their primary tumors, suggesting that these mutations were acquired in the course of the disease. In addition, 7 genes (ALK, BRCA1, CKD4, FGFR2, FGFR3, MUC16 and ZNF217) in the recurrent tumors (n = 8) of the patients with relapse were potentially druggable.
Conclusions
The discovery of genomic alterations associated with recurrence in NPC may serve as prognostic or predicting gene signatures of high-risk patients. Targeted therapy is available in some of the genomic alterations and should be considered in future clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K-P. Tse, S-J. Chen, Y-T. Yang, T. Tang, T.T. Yip, K.T. Tan: Full/Part-time employment: ACT Genomics. All other authors have declared no conflicts of interest.