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

doi:10.1016/j.ccr.2011.11.005

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

Global Public Health

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	810-817
Number of pages	8
Journal	Cancer Cell
Volume	20
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2011.11.005
State	Published - Dec 13 2011

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2011.11.005

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title = "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.",

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

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AU - Snuderl, Matija

AU - Fazlollahi, Ladan

AU - Le, Long P.

AU - Nitta, Mai

AU - Zhelyazkova, Boryana H.

AU - Davidson, Christian J.

AU - Akhavanfard, Sara

AU - Cahill, Daniel P.

AU - Aldape, Kenneth D.

AU - Betensky, Rebecca A.

AU - Louis, David N.

AU - Iafrate, A. John

PY - 2011/12/13

Y1 - 2011/12/13

N2 - 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.

AB - 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.

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Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma

Abstract

ASJC Scopus subject areas

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