Introduction: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. The clinical outcomes of patients with early stage disease have improved significantly in recent years, but a substantial number of patients would develop recurrent disease and it is the major cause of mortality. Understanding the genetic mechanism of relapse may help develop novel treatment modalities and strategies for this group of patients. This study aims to compare and identify the genetic alterations in primary and recurrent NPC by next-generation sequencing.

Materials and Methods: The archived paired samples of 7 primary and 8 matched relapsed tumor tissues from seven NPC patients (one with 2 relapsed points) who developed recurrence after treatment were retrieved. Using deep targeted next-generation sequencing, we evaluated a panel of 440 genes in these 15 NPC samples. Genomic alterations found in cancer samples at the first diagnosis (primary tumors) were compared with those found in the relapsed tissues (progression after treatment).

Results: Overall, we found that all patients showed a number of mutations in both the primary tumors and relapsed tissues. The most frequently mutated genes were MUC16 (85.7%), ADAMTS9 (80%), MITF (73.3%), ADAMTSL1 (73.3%), PTPRD (66.7%), TEK (66.7%), FOXP1 (53.3%) and IRS2 (53.3%). We observed that MCL1(42.9%), SOX2 (42.9%) and PIK3C2G (28.6%) mutations were only found in the primary tumor. Comparing to the primary tumors, all patients acquired new mutations in the relapsed tissues. The seven patients have each acquired 6, 13, 14, 20, 29, 31 and 35 new genomic alterations respectively. PAX5 (42.9%), PIK3CA (42.9%), CREBBP (28.6%), DPYD (28.6%), FANCG (28.6%), BIRC2 (28.6%), BIRC3 (28.6%) and PTEN (28.6%) were the most frequently detected gene mutations newly acquired in the relapsed tissues.

Conclusion: This study demonstrated that mutation events might be present at diagnosis or arise during cancer treatment. The finding that all primary tumors harboring a number of mutations could explain the subsequent relapse and might therefore warrant more precise therapies. Tumor relapse is associated with the acquisition of additional gene mutations, particularly copy number variant deletion in PAX5 gene and single nucleotide variant missense in PIK3CA gene. Our results revealed substantial discordances between the primary tumors and recurrences, stressing the need for analysis of the relapsed tissues. Further analysis of these mutations and the study of their downstream protein may be useful for the development of novel treatment for this group of patients.

Citation Format: William C. Cho, Yi-Ting Yang, Kein T. Tan, Victor W. Ma, Wah Cheuk, Roger K. Ngan, Shu-Jen Chen. New genomic alterations are frequently detected in recurrent nasopharyngeal carcinoma compared with the primary tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5142.