Genomic characterization reveals potential biomarkers in nasopharyngeal carcinoma patients with relapse

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.

KEYWORDS:

• Clinically relevant genomic alteration
• nasopharyngeal carcinoma
• next-generation sequencing
• prognostic biomarker
• relapse

Article highlights

• This study demonstrates a number of genomic alterations associated with overall survival and thus may serve as prognosis biomarkers of high-risk patients.

• Most importantly, our research discovered several clinically relevant genomic alterations for which targeted drugs or experimental agents are available.

• Comprehensive genomic profiling of the primary and recurrent tumors may assist in selecting optimal management and inform therapeutic options beyond the standard of care testing for NPC patients.

Declaration of interest

Ka-Po Tse, Yi-Ting Yang, Timothy T. Yip, Kien T. Tan, and Shu-Jen Chen have declared employment at ACT Genomics Co. Ltd. The authors have no other relevant affiliations or financial involvement with any other organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception and design: William C. Cho; Provision of study material or patients: Wah Cheuk, Roger K. Ngan, William C. Cho, Victor W. Ma; Collection and/or assembly of the data: Roger K. Ngan, William C. Cho, Wah Cheuk; Methodology, analysis, and interpretation of the data: Ka-Po Tse, William C. Cho, Kien T. Tan, Yi-Ting Yang; Drafting of the paper: William C. Cho; Drafting-review and final approval of the paper: William C. Cho, Ka-Po Tse, Roger K. Ngan, Wah Cheuk, Victor W. Ma, Yi-Ting Yang, Timothy T. Yip, Kien T. Tan, Shu-Jen Chen

Additional information

Funding

This paper was not funded.