Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing.

Abstract

OBJECTIVES:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Bian Wu, Liangfang Shen, Gang Peng, Yingqiang Li, Zhiyuan Zhou, Jingao Li, Xiaodong Huang, Qin Zhou, Hongguo Jiang, Jing Huang, Qian Ding, Zhanjie Zhang, You Qin, Xiaohua Hong, Liangliang Shi, Zhenwei Zou, Jing Yao, Jing Zhang, Danni Liu, Chao Wan, Gang Wu, Lele Song, Shifu Chen, Junlin Yi, Kunyu Yang
• Journal: Oral oncology (Oral Oncol) Vol. 135 Pg. 106218 (12 2022) ISSN: 1879-0593 [Electronic] England
• PMID: 36332446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• B7-H1 Antigen
• RBM38 protein, human
• RNA-Binding Proteins

Topics

• Child
• Female
• Humans
• Male
• B7-H1 Antigen (metabolism)
• Mutation
• Nasopharyngeal Carcinoma (genetics, pathology)
• Nasopharyngeal Neoplasms (genetics, pathology)
• Neoplasm Recurrence, Local
• RNA-Binding Proteins (genetics)
• Exome Sequencing