AUTHOR=Yuan Guangwen , Song Jinge , Li Ning , Song Qianqian , Li Yifei , Du Yingxi , Wang Xiaobing , Jiao Yuchen , Wu Lingying 

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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01707

DOI=10.3389/fonc.2020.01707

ISSN=2234-943X

ABSTRACT=<sec><title>Purpose</title><p>Gynecological melanomas (GMs) are rare tumors with a poor prognosis. Here, we performed exome sequencing to generate the mutational landscape of GMs.</p></sec><sec><title>Methods</title><p>Next-generation sequencing was carried out on mucosal melanoma samples (<italic>n</italic> = 35) obtained from gynecological sites. The alternative telomere lengthening (ALT) phenotype was verified by fluorescence <italic>in situ</italic> hybridization and the C-circle assay. Immunohistochemistry was performed to detect ATRX protein. Copy number variations in <italic>TERT</italic> were detected by droplet digital polymerase chain reaction.</p></sec><sec><title>Results</title><p>In the 58 formalin-fixed paraffin-embedded samples, we identified 33 (56.9%) ALT-positive cases, with 23 showing loss of ATRX protein. <italic>TERT</italic> promoter mutation was not detected in GMs (<italic>n</italic> = 40), but copy number variations in the <italic>TERT</italic> region were observed in 20% (7/35) of the samples. <italic>TERT</italic> amplification was mutually exclusive with ALT (<italic>P</italic> &lt; 0.05). Kaplan–Meier revealed that ALT relative to <italic>TERT</italic> amplification was associated with longer overall survival in GM patients without metastasis.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>