J Cancer 2019; 10(2):488-493. doi:10.7150/jca.26967 This issue

Research Paper

Potential Mutations in Uveal Melanoma Identified Using Targeted Next-Generation Sequencing

Jiayi Yu#, Xiaowen Wu#, Junya Yan, Jinyu Yu, Ting Yin, Jie Dai, Meng Ma, Tianxiao Xu, Huan Yu, Longwen Xu, Lu Yang, Zhiyuan Cheng, Zhihong Chi, Xinan Sheng, Lu Si, Chuanliang Cui, Jun Guo, Yan Kong

Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, No. 52 Fucheng Road, Haidian District, Beijing, China, 100142.
#Contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Yu J, Wu X, Yan J, Yu J, Yin T, Dai J, Ma M, Xu T, Yu H, Xu L, Yang L, Cheng Z, Chi Z, Sheng X, Si L, Cui C, Guo J, Kong Y. Potential Mutations in Uveal Melanoma Identified Using Targeted Next-Generation Sequencing. J Cancer 2019; 10(2):488-493. doi:10.7150/jca.26967. Available from https://www.jcancer.org/v10p0488.htm

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Background/objective: Uveal melanoma (UM) is the most common intraocular malignancy and has a high tendency to metastasize to the liver. Although primary tumours can be successfully treated, there is currently no effective treatment for metastatic UM. To gain insight into the genetics of UM, we performed the targeted next-generation sequencing (NGS) of UM samples from a non-Caucasian population.

Methods: This study included tumour samples and blood samples from 107 UM patients at Peking University Cancer Hospital & Institute. Clinical data were collected. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) specimens. Using the HaloPlex Target Enrichment System (Agilent Technologies), NGS was performed to investigate mutations in a 35-gene panel composed of cancer-related genes.

Results: Recurrent coding mutations were found in the known UM drivers GNAQ and GNA11. FOXO1, PIK3R1 and HIF1A were also found to harbour somatic mutations in more than 20% of patients, a result that may indicate previously undescribed associations between these genes and UM pathogenesis. Patients with HIF1A and FOXO1 mutations exhibited worse overall survival (OS). In multivariate analysis, FOXO1 mutation was an independent prognostic factor for OS (P<0.05) that was associated with an increase in the risk ratio by a factor of 1.35. Notably, we found that HIF1A and FOXO1 mutations were associated with metastatic transformation of UM (P<0.05 and P<0.001, respectively).

Conclusion: Our findings from analyses of targeted NGS data shed new light on the molecular genetics of UM and facilitate the exploration of mutations associated with metastatic potential.

Keywords: uveal melanoma, metastasis, FOXO1, HIF1A.