Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor

Mol Med. 2022 Mar 14;28(1):34. doi: 10.1186/s10020-022-00454-z.

Abstract

Background: IDH-mutant astrocytoma and oligodendroglioma have an indolent natural history and are recognized as distinct entities of neoplasms. There is little knowledge on the molecular differences between IDH-mutant astrocytoma and oligodendroglioma grade 2. Therefore, we investigated the multiomics and clinical data regarding these two types of tumors.

Method: In silico analyses were performed around mRNA, somatic mutations, copy number alternations (CNAs), DNA methylation, microRNA (miRNA), epigenetics, immune microenvironment characterization and clinical features of the two types of gliomas. A diagnostic model incorporating tumor purity was further established using machine learning algorithms, and the predictive value was evaluated by receiver operative characteristic curves.

Results: Both types of gliomas shared chromosomal instability, and astrocytomas exhibited increased total CNAs compared to oligodendrogliomas. Oligodendrogliomas displayed distinct chromosome 4 (chr 4) loss, and subtyping of chr 7 gain/chr 4 loss (+ 7/- 4) presented the worst survival (P = 0.004) and progression-free interval (PFI) (P < 0.001). In DNA damage signatures, oligodendroglioma had a higher subclonal genome fraction (P < 0.001) and tumor purity (P = 0.001), and astrocytoma had a higher aneuploidy score (P < 0.001). Furthermore, astrocytomas exhibited inflamed immune cell infiltration, activated T cells and a potential response to immune checkpoint inhibitors (ICIs), while oligodendrogliomas were more homogeneous with increased tumor purity and decreased aggression. The tumor purity-involved diagnostic model exhibited great accuracy in identifying astrocytoma and oligodendroglioma.

Conclusion: This study addresses the similarities and differences between IDH-mutant astrocytoma and oligodendroglioma grade 2 and facilitates a deeper understanding of their molecular features, immune microenvironment, tumor purity and prognosis. The diagnostic tool developed using machine learning may offer support for clinical decisions.

Keywords: Astrocytoma; IDH-mutant; Oligodendroglioma; Tumor microenvironment; Tumor purity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma* / diagnosis
  • Astrocytoma* / genetics
  • Astrocytoma* / pathology
  • Brain Neoplasms* / diagnosis
  • Chromosome Deletion
  • Genomics
  • Glioma* / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Mutation
  • Oligodendroglioma* / diagnosis
  • Oligodendroglioma* / genetics
  • Oligodendroglioma* / pathology
  • Tumor Microenvironment / genetics

Substances

  • Isocitrate Dehydrogenase