TERT copy gain predicts the outcome of high-dose interferon α-2b therapy in acral melanoma

Abstract

Background: Asian populations are more likely to develop acral melanoma (AM) than Caucasians. The high-dose interferon (HD-IFN) α-2b regimen is the main adjuvant treatment for AM. TERT encodes the catalytic subunit of telomerase reverse transcriptase, which plays an important role in melanoma. Frequent TERT mutation and increased TERT gene expression have been described in AM. Our study aimed to investigate the status and the clinical significance of TERT copy number in a large cohort of patients with AM and to analyze the relationship between TERT copy number gain and the efficiency of HD-IFN. Patients and methods: A total of 573 melanoma samples were retrospectively collected and analyzed for TERT copy number via Sanger sequencing. Clinical data of patients were also collected. Results: TERT copy gain (copy number >2) was detected in 257 of the 573 patients with AM (44.9%). Of the 573 patients, 81 (14.1%) had a high copy gain (copy number >4). Patients with ulceration showed a significantly higher copy gain rate of TERT compared to the patients without ulceration (P=0.028). Patients with a tumor thicker than 4 mm also had a higher copy number rate of TERT than those with <4 mm (P=0.048). Our results showed that the overall survival (OS) was not significantly different between patients with and without TERT copy gain (P=0.890). However, among the 278 patients who received an HD-IFN regimen, Kaplan–Meier survival analysis demonstrated a significant correlation between TERT copy gain and relapse-free survival (RFS) (P=0.008). In addition, multivariate Cox regression assays validated TERT copy gain to be an independent prognostic factor of RFS for patients with AM undergoing HD-IFN therapy (hazard ratio =1.50; P=0.019). Conclusion: The copy number status of TERT might be a predictor for HD-IFN efficacy, but it is not a prognostic factor of OS in patients with AM.