Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro

Cancer Res. 2013 Sep 15;73(18):5834-44. doi: 10.1158/0008-5472.CAN-13-1299. Epub 2013 Jul 25.

Abstract

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Brain / cytology
  • Brain / metabolism*
  • Brain Neoplasms / classification
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Lineage*
  • Gene Expression Profiling*
  • Glioma / classification
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase / physiology
  • Phenotype
  • Proteins / physiology
  • RNA, Messenger / genetics
  • RNA, Untranslated
  • Real-Time Polymerase Chain Reaction
  • Retinoblastoma Protein / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Biomarkers, Tumor
  • Gt(ROSA)26Sor non-coding RNA, mouse
  • Proteins
  • RNA, Messenger
  • RNA, Untranslated
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • Pten protein, mouse