Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
Xi Yuan , Tianshi Que , Guozhong Yi , Zhiyong Li , Haojie Zheng , Yawei Liu , Xiaoxuan Wang , Xing Zhang , Guanglong Huang
Background: Glioma is commonly described as a disease of neuroglial cell proliferation. And the gene related to cell cycle pathway alter frequently in glioma including CDKN2A/B, CDK4 and CDK6. CDKN2A/B homozygous deletion is proved to be associated with worse survival in IDH-mut gliomas and meningiomas. However, the correlation between CDK4/6 amplification and the prognosis of glioma remains unclear. Herein, we explored the distribution of CDK4/6 alterations and whether they are the prognostic biomarker of glioma. Methods: A total of 90 patients with adult-type diffuse glioma were enrolled to this retrospective study from our center. Whole genome sequencing (WES) was performed to identify the mutations of the cohort. Results:CDK4 and CDK6 amplified in 17 (18.9%) and 12 (13.3%) patients, respectively. Four patients harbored both CDK4 and CDK6 amplification. The Cox multivariate regression revealed only CDK6 amplification was the independent factor (HR 4.0, 95% CI 1.1-15.2, p=0.041) of overall survival (OS). Interestingly, CDK6 amplification occurred easier in female and trended to be co-mutant with CDKN2A/B homozygous deletion. CDK6 amplification was found to be significantly associated with shorter OS (p<0.05) of glioblastoma (GBM). Although TERTp was not related to the OS of GBM according to TCGA, patients harboring both TERTp and CDK6 amplification had the significant worst OS (p<0.001). Conclusions: Our study compared the mutational characteristics of gliomas with CDK4/6 alterations and demonstrated the potential prognostic value of CDK6 amplification, and provide the new basis of precise diagnosis and treatment in gliomas.
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Abstract Disclosures
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