Sign in Subscribe
Universities and colleges

Comparative Analyses of Gene Copy Number and mRNA Expression in Glioblastoma Multiforme Tumors and Xenografts

Strategic Insights

— 1 min read

Researchers have made significant progress in understanding the molecular characteristics of glioblastoma multiforme (GBM) tumors by developing model systems that recapitulate the molecular heterogeneity observed among GBM tumors. In a study published in Neuro-oncology, scientists in the United States profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX). The results showed that the predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. The study also identified novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1, that are amplified and overexpressed in GBM tumors.

Key Takeaways:

  • The study developed a model system that recapitulates the molecular heterogeneity observed among GBM tumors, which will expedite the testing of targeted molecular therapeutic strategies for GBM treatment.
  • The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature.
  • Genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, were observed at frequencies similar to those detected in TCGA GBM tumors.
  • Novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1, were identified as being amplified and overexpressed in GBM tumors.
  • The transcriptional signature of GBMX tumors was stable over multiple subcutaneous passages and was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC).
  • Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1.

Statistics:

  • 21 independent GBM tumor lines were profiled in the study.
  • The study observed genomic amplification and overexpression of 6 known GBM oncogenes and 5 novel genes in GBM tumors.
  • The transcriptional signature of GBMX tumors was stable over multiple subcutaneous passages.
  • The study identified a total of 12 genes that are overexpressed in GBM tumors, including 6 MRC cancer genes.

Sources:

  • J.G. Hodgson et al. (2009) Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts. Neuro-oncology, 11(5), 477-487.
  • University of California, Department of Neurological Surgery.

Read more