Molecular characteristics are essential for the classification and grading of glioma. However, the majority of current understanding is based on public databases that might not accurately reflect the Asian population. Here, we studied the genetic landscape of Chinese glioma patients in hope to provide strong rationales for future molecular classification and prognosis of glioma.
Tissue samples from 81 glioma patients of which 21 (26%) were astrocytoma (A) and oligodendroglioma (O), 16 (20%) were anaplastic astrocytoma/oligodendroglioma (AO/AA), 32 (40%) were Glioblastoma (GBM), and 8 (10%) were diffuse midline glioma underwent next-generation sequencing with Acornmed panel including 808 cancer-relevant genes.
We identified currently established molecular pathologic markers of glioma, including TP53 (41%),TERT (34%), IDH1/2 (30%), PTEN (19%), ATRX (18%), EGFR (16%), H3F3A (10%) and BRAF (6%). IDH mutations were frequent in A and O and were a major discriminate of biologic class (P=0.002). IDH-mutant A/O (grades II) were characterized by MGMT methylation, ATRX, and CIC mutations. AO/AA (grades III) were also IDH1/2-mutant, but instead are characterized by TP53, BRAF, and FUBP1 mutations. GBM typically lacked IDH1/2 mutations and demonstrated EGFR, PTEN, TP53, PIK3CA, and CDKN2A alterations, and TERT promoter mutations. Copy number variations as EGFR, PDGFRA, MET, KIT, which were also significantly associated with GBM but not used for clinical classification (P=0.001). Clinically actionable genetic alterations were detected in 80.95%, 81.25%, and 93.75% of A/O, AA/AO, and GBM, respectively.
We demonstrate that genes characterize the distinction between these pathologic subsets. These results further define molecular subsets of gliomas which may potentially be used for patient stratification and suggest potential targets for treatment.
The authors.
Has not received any funding.
M. Li, H. Cheng, H. Wang, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd. All other authors have declared no conflicts of interest.