Telomere Maintenance Associated Mutations in the Genetic Landscape of Gynecological Mucosal Melanoma

作者：Guangwen Yuan, Jinge Song, Ning Li, Qianqian Song, Yifei Li, Yingxi Du, Xiaobing Wang, Yuchen Jiao, Lingying Wu · 发表于：Frontiers in Oncology · 年份：2020 · DOI：10.3389/fonc.2020.01707 · 被引用次数：7 · 研究领域：Cancer Genomics and Diagnostics、Cancer Cells and Metastasis、Immunotherapy and Immune Responses

Purpose: Gynecological melanomas (GMs) are rare tumors with a poor prognosis. Here, we performed exome sequencing to generate the mutational landscape of GMs. Methods: Next-generation sequencing (NGS) was carried out on mucosal melanoma samples (n = 35) obtained from gynecological sites. The Alternative telomere lengthening (ALT) phenotype was verified by fluorescence in situ hybridization (FISH) and the C-circle assay. Immunohistochemistry (IHC) was performed to detect ATRX protein. Copy number variations in TERT were detected by droplet digital PCR (ddPCR). Results: In the 58 formalin-fixed-paraffin-embedded (FFPE) samples, we identified 33 (56.9%) ALT-positive cases with 23 showing loss of ATRX protein. TERT promoter mutation was not detected in GMs (n = 40), but copy number variations in the TERT region were observed in 20% (7/35) of the samples. TERT amplification was mutually exclusive with ALT (P < 0.05). Kaplan-Meier revealed that ALT relative to TERT amplification was associated with longer overall survival (OS) in GM patients without metastasis. Conclusion: These findings indicate that telomere maintenance mechanisms (TMMs) play a critical role in the tumorigenesis of GMs and may aid in the prediction of clinical prognosis and the development of targeted therapy for the treatment of GM.