Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma

Matija Snuderl, Ladan Fazlollahi, Long P. Le, Mai Nitta, Boryana H. Zhelyazkova, Christian J. Davidson, Sara Akhavanfard, Daniel P. Cahill, Kenneth D. Aldape, Rebecca A. Betensky, David N. Louis, A. John Iafrate

Research output: Contribution to journalArticlepeer-review


Tumor heterogeneity has been implicated in tumor growth and progression as well as resistance to therapy. We present an example of genetic heterogeneity in human malignant brain tumors in which multiple closely related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to three different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell. The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies.

Original languageEnglish (US)
Pages (from-to)810-817
Number of pages8
JournalCancer Cell
Issue number6
StatePublished - Dec 13 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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