Journal Article

Comparative genomic landscape of lower-grade glioma and glioblastoma

Li, Kun, Jia, Xiaodong, Tian, Conghui, Yan, Lili, Jia, Qingbin, Zheng, Juan, Yi, Lili, Gu, Mingliang, Sun, Xinxin

2024

Overview

Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1 -wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10 , for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Biology and Life Sciences / Biomarkers / Biomarkers, Tumor - genetics / Brain cancer / Brain Neoplasms - genetics / Brain Neoplasms - pathology / Cadherins - genetics / Cancer / Cell cycle / Classification / Comparative analysis / Copy number / DNA Copy Number Variations / Exome Sequencing / Female / Genes / Genetic aspects / Genetic testing / Genomes / Genomics / Genomics - methods / Glioblastoma / Glioblastoma - genetics / Glioblastoma - pathology / Glioblastoma multiforme / Glioma / Glioma - genetics / Glioma - pathology / Gliomas / Humans / Isocitrate Dehydrogenase - genetics / Male / Medical prognosis / Medicine and Health Sciences / Middle Aged / Mutation / Neoplasm Grading / p53 Protein / Prognosis / Protocadherins / Research and Analysis Methods / Statistical analysis / Survival analysis / Telomerase - genetics / Therapeutic targets / Tumor Suppressor Protein p53 - genetics / Tumors / Whole genome sequencing / X-linked Nuclear Protein - genetics / Young Adult