Telomere Maintenance Associated Mutations in the Genetic Landscape of Gynecological Mucosal Melanoma
Telomere Maintenance Associated Mutations in the Genetic Landscape of Gynecological Mucosal Melanoma
复制标题
妇科粘膜黑色素瘤遗传景观中端粒维持相关的突变。
DOI：
10.3389/fonc.2020.01707
复制
发表时间：
2020-09-02
影响因子：
4.7
通讯作者：
Wu, Lingying
中科院分区：
文献类型：
--
作者：
Yuan, Guangwen;Song, Jinge;Wu, Lingying
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 was carried out on mucosal melanoma samples (n= 35) obtained from gynecological sites. The alternative telomere lengthening (ALT) phenotype was verified by fluorescencein situhybridization and the C-circle assay. Immunohistochemistry was performed to detect ATRX protein. Copy number variations inTERTwere detected by droplet digital polymerase chain reaction. Results In the 58 formalin-fixed paraffin-embedded samples, we identified 33 (56.9%) ALT-positive cases, with 23 showing loss of ATRX protein.TERTpromoter mutation was not detected in GMs (n= 40), but copy number variations in theTERTregion were observed in 20% (7/35) of the samples.TERTamplification was mutually exclusive with ALT (P< 0.05). Kaplan-Meier revealed that ALT relative toTERTamplification was associated with longer overall survival in GM patients without metastasis. Conclusion These findings indicate that telomere maintenance mechanisms 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.
