Clinical sequencing reveals diagnostic, therapeutic, and prognostic biomarkers for adult-type diffuse gliomas
Zhenyan Li,
Zhenghao Deng,
Fangkun Liu,
Chuntao Li,
Kui Yang,
Xuan Gong,
Songshan Feng,
Yu Zeng,
Hongshu Zhou,
Fan Fan,
Chengke Luo,
Zhixiong Liu,
Mingyu Zhang
Affiliations
Zhenyan Li
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Zhenghao Deng
Department of Pathology, Xiangya Hospital Central South University, Changsha, 410008, China
Fangkun Liu
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Chuntao Li
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Kui Yang
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Xuan Gong
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Songshan Feng
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Yu Zeng
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Hongshu Zhou
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Fan Fan
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Chengke Luo
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Zhixiong Liu
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China
Mingyu Zhang
Department of Neurosurgery, Xiangya Hospital Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, 410008, China; Corresponding author. Department of Neurosurgery, Xiangya Hospital Central South University, No.87 Xiangya Road, Changsha, 410008, China.
Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.
