Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing.
Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing.
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DOI：
10.1016/j.oraloncology.2022.106218
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发表时间：
2022-11
期刊：
影响因子：
4.8
通讯作者：
Bian Wu;Liang Shen;G. Peng;Yingqiang Li;Zhiyuan Zhou;Jingao Li;Xiaodong Huang;Qin Zhou;Hongguo Jiang;Jing Huang;Q. Ding;Zhanjie Zhang;You Qin;X. Hong;Liangliang Shi;Z. Zou;Jing Yao;Jing Zhang;Danni Liu;Chao Wan;Gang Wu;Lele Song;Shifu Chen;J. Yi;Kunyu Yang
中科院分区：
文献类型：
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作者：
Bian Wu;Liang Shen;G. Peng;Yingqiang Li;Zhiyuan Zhou;Jingao Li;Xiaodong Huang;Qin Zhou;Hongguo Jiang;Jing Huang;Q. Ding;Zhanjie Zhang;You Qin;X. Hong;Liangliang Shi;Z. Zou;Jing Yao;Jing Zhang;Danni Liu;Chao Wan;Gang Wu;Lele Song;Shifu Chen;J. Yi;Kunyu Yang
目的虽然成人鼻咽癌（aNPC）的发生与多种遗传和表观遗传因素有关，但儿童鼻咽癌（pNPC）的缺乏阻碍了人们对该疾病生物学的认识和合理的治疗方法。我们的目的是确定pNPC的分子特征。材料和方法pNPC原发肿瘤与配对的血液样品收集和测序使用全外显子组测序。样本收集自中国的四个三级学术医学中心。结果pNPC中C9 orf 84（20%）、ZFHX 4（16.7%）、ZC 3 H6（16.7%）、RBM 38（16.7%）等基因突变频率较高。拷贝数分析显示HLA II类基因在6p21.32（63.3%）处高度重复获得/扩增，而TOLLIP在11p15.5（20%）处丢失。在pNPC中首次发现了复发NUTM 1（16.7%）融合变异体。我们还研究了生殖系基因组特征，并显示30例pNPC患者中有8例（26.7%）携带已知癌症易感基因中的生殖系致病性和/或可能的致病性变体。多维比较表明，与aNPC相比，pNPC可能表现出不同的基因组谱。此外，pNPC表现出明显高于aNPC的PD-L1表达水平（PD-L1表达> 50%的患者百分比：92.0%vs 32.1%），表明免疫治疗的可能性很高。结论我们的结果提供了第一个深入了解pNPC的分子基础，并可能为这种罕见疾病提供新的靶点和治疗方法，如免疫治疗。
ObjectivesWhile 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 MethodspNPC 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.ResultsSeveral genes such asC9orf84(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 ofTOLLIPat 11p15.5 (20 %). RecurrentNUTM1(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.ConclusionOur 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.