AUTHOR=Deng Jiaojiao , Sun Shuchen , Chen Jiawei , Wang Daijun , Cheng Haixia , Chen Hong , Xie Qing , Hua Lingyang , Gong Ye 

TITLE=TERT Alterations Predict Tumor Progression in De Novo High-Grade Meningiomas Following Adjuvant Radiotherapy

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.747592

DOI=10.3389/fonc.2021.747592

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Adjuvant radiotherapy (RT) is one of the most commonly used treatments for <italic>de novo</italic> high-grade meningiomas (HGMs) after surgery, but genetic determinants of clinical benefit are poorly characterized.</p></sec><sec><title>Objective</title><p>We describe efforts to integrate clinical genomics to discover predictive biomarkers that would inform adjuvant treatment decisions in <italic>de novo</italic> HGMs.</p></sec><sec><title>Methods</title><p>We undertook a retrospective analysis of 37 patients with <italic>de novo</italic> HGMs following RT. Clinical hybrid capture-based sequencing assay covering 184 genes was performed in all cases. Associations between tumor clinical/genomic characteristics and RT response were assessed. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan–Meier method.</p></sec><sec><title>Results</title><p>Among the 172 HGMs from a single institution, 42 cases (37 WHO grade 2 meningiomas and five WHO grade 3 meningiomas) were identified as <italic>de novo</italic> HGMs following RT. Only <italic>TERT</italic> mutations [62.5% C228T; 25% C250T; 12.5% copy number amplification (CN amp.)] were significantly associated with tumor progression after postoperative RT (adjusted <italic>p</italic> = 0.003). Potential different somatic interactions between <italic>TERT</italic> and other tested genes were not identified. Furthermore, <italic>TERT</italic> alterations (<italic>TERT</italic>-alt) were the predictor of tumor progression (Fisher’s exact tests, <italic>p</italic> = 0.003) and were associated with decreased PFS (log-rank test, <italic>p</italic> = 0.0114) in <italic>de novo</italic> HGMs after RT.</p></sec><sec><title>Conclusion</title><p>Our findings suggest that <italic>TERT</italic>-alt is associated with tumor progression and poor outcome of newly diagnosed HGM patients after postoperative RT.</p></sec>