ABSTRACT

Background

Although the majority of nasopharyngeal carcinoma (NPC) patients demonstrate favorable outcomes after radiotherapy and/or chemotherapy, about 8–10% of patients will develop recurrent disease, and genomic alterations (GAs) associated with the recurrence are unclear.

Methods

This study investigated the GAs in the paired primary tumors and recurrent tumors of 7 NPC patients with relapse, as well as the primary tumors of 15 NPC patients without relapse by deep targeted next-generation sequencing on 440 cancer-related genes.

Results

BRCA1 and TP53 mutations were significantly enriched in patients with relapse (P = 0.021 and P = 0.023, respectively). Survival analysis revealed that the GAs of TP53, ZNF217, VEGFB, CDKN1B, GNAS, PRDM1, and MEN1 were associated with significantly shorter overall survival. The GAs of the tumor also altered after treatment in the relapsed group, and five genes (CDK4, FGFR3, ALK, BRCA1, and CHEK2) in the recurrent tumors were potentially druggable.

Conclusions

The discovery of GAs associated with recurrence or survival in NPC may serve as potential prognostic gene signatures of high-risk patients. Targeted therapies are available in some of the clinically relevant GAs and may be considered in future clinical trials. Given the limitation of the sample size, validation by a larger cohort is warranted.

中文翻译：

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基因组特征揭示鼻咽癌复发患者的潜在生物标志物

摘要

背景

尽管大多数鼻咽癌 (NPC) 患者在放疗和/或化疗后表现出良好的结果，但约 8-10% 的患者会出现复发，并且与复发相关的基因组改变 (GA) 尚不清楚。

方法

本研究通过对 440 个癌症相关基因的深度靶向二代测序，研究了 7 名复发鼻咽癌患者的原发肿瘤和复发肿瘤配对中的 GAs，以及 15 名未复发鼻咽癌患者的原发肿瘤中的 GAs。

结果

BRCA1和TP53突变在复发患者中显着富集（分别为P = 0.021 和P = 0.023）。生存分析显示TP53、ZNF217、VEGFB、CDKN1B、GNAS、PRDM1和MEN1 的GA与显着更短的总生存期相关。复发组治疗后肿瘤的 GA 也发生了变化，复发肿瘤中的五个基因（CDK4、FGFR3、ALK、BRCA1和CHEK2）可能是可药物治疗的。

结论

与 NPC 复发或存活相关的 GA 的发现可能作为高危患者潜在的预后基因特征。在一些临床相关的 GA 中可以使用靶向治疗，并且可能会在未来的临床试验中考虑。鉴于样本量的限制，有必要通过更大的队列进行验证。