Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing

•We first reported the somatic and germline genetic aberrations in pNPC.•Patients with pNPC exhibited high level of PD-L1 expression.•Our results provide a deeper understanding of molecular genetics of pNPC. While a number of genetic and epigenetic events contributing to adult nasopharyngeal carcinomas (aNPC) development has been established, the scarcity of pediatric nasopharyngeal carcinoma (pNPC) hinders the understanding of the biology of the disease and rational treatment approach. We aim to identify the molecular characteristics of pNPC. pNPC primary tumors with paired blood samples were collected and sequenced using whole-exome sequencing. Samples were collected from four tertiary academic medical centers in China. A total of 30 patients (25 male and 5 female) with pathologically confirmed NPC under the age of 20 were enrolled. Several genes such as C9orf84 (20 %), ZFHX4 (16.7 %), ZC3H6 (16.7 %), RBM38 (16.7 %) were frequently mutated in pNPC. Copy number analysis revealed highly recurring gain/amplification of the HLA class II genes at 6p21.32 (63.3 %) and losses of TOLLIP at 11p15.5 (20 %). Recurrent NUTM1 (16.7 %) fusion variants were found for the first time with pNPC. We also investigated germline genomic signatures and showed 8 of 30 (26.7 %) of the pNPC patients carrying germline pathogenic and/or likely pathogenic variants in known cancer-predisposing genes. Multi-dimensional comparison suggested that pNPC might exhibit distinct genomic profile compared to aNPC. In addition, pNPC exhibited significantly elevated level of PD-L1 expression than aNPC (percent of patients with >50 % PD-L1 expression: 92.0 % vs 32.1 %), suggesting high possibility of benefit from immunotherapy. Our results provide the first insight into the molecular basis of pNPC, and might offer novel targets and therapeutic approaches such as immunotherapy for this rare disease.