Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma
- PMID: 22137795
- DOI: 10.1016/j.ccr.2011.11.005
Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma
Abstract
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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Comment in
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Many tumors in one: a daunting therapeutic prospect.Cancer Cell. 2011 Dec 13;20(6):695-7. doi: 10.1016/j.ccr.2011.11.018. Cancer Cell. 2011. PMID: 22172718
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Genetics: United colors of glioblastoma.Nat Rev Clin Oncol. 2012 Jan 10;9(2):68. doi: 10.1038/nrclinonc.2011.202. Nat Rev Clin Oncol. 2012. PMID: 22231761 No abstract available.
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