Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma

被引：547

作者：

Snuderl, Matija ^{[1
,2
]}

Fazlollahi, Ladan ^{[1
,2
]}

Le, Long P. ^{[1
,2
]}

Nitta, Mai ^{[1
,2
]}

Zhelyazkova, Boryana H. ^{[1
,2
]}

Davidson, Christian J. ^{[1
,2
]}

Akhavanfard, Sara ^{[1
,2
]}

Cahil, Daniel P. ^{[3
,6
]}

Aldape, Kenneth D. ^{[4
,6
]}

Betensky, Rebecca A. ^{[5
]}

Louis, David N. ^{[1
,2
]}

Iafrate, A. John ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA 02114 USA

[3] Dept Neurosurg, Houston, TX 77030 USA

[4] Dept Pathol, Houston, TX 77030 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

来源：

CANCER CELL | 2011年 / 20卷 / 06期

关键词：

CANCER; HETEROGENEITY; EVOLUTION; VEGFR2; KIT;

D O I：

10.1016/j.ccr.2011.11.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：810 / 817

页数：8

共 22 条

[11] Tumour evolution inferred by single-cell sequencing [J].

Navin, Nicholas ;

Kendall, Jude ;

Troge, Jennifer ;

Andrews, Peter ;

Rodgers, Linda ;

McIndoo, Jeanne ;

Cook, Kerry ;

Stepansky, Asya ;

Levy, Dan ;

Esposito, Diane ;

Muthuswamy, Lakshmi ;

Krasnitz, Alex ;

McCombie, W. Richard ;

Hicks, James ;

Wigler, Michael .

NATURE, 2011, 472 (7341) :90-U119

[12] Inferring tumor progression from genomic heterogeneity [J].

Navin, Nicholas ;

Krasnitz, Alexander ;

Rodgers, Linda ;

Cook, Kerry ;

Meth, Jennifer ;

Kendall, Jude ;

Riggs, Michael ;

Eberling, Yvonne ;

Troge, Jennifer ;

Grubor, Vladimir ;

Levy, Dan ;

Lundin, Par ;

Maner, Susanne ;

Zetterberg, Anders ;

Hicks, James ;

Wigler, Michael .

GENOME RESEARCH, 2010, 20 (01) :68-80

[13]

Nicholas M Kelly, 2007, Expert Rev Anticancer Ther, V7, pS23, DOI 10.1586/14737140.7.12s.S23

[14] Molecular Heterogeneity in Glioblastoma: Therapeutic Opportunities and Challenges [J].

Nicholas, M. Kelly ;

Lukas, Rimas V. ;

Chmura, Steven ;

Yamini, Bakhtihar ;

Lesniak, Maciej ;

Pytel, Peter .

SEMINARS IN ONCOLOGY, 2011, 38 (02) :243-253

[15]

Okada Y, 2003, CANCER RES, V63, P413

[16] Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas [J].

Puputti, Marjut ;

Tynninen, Olli ;

Sihto, Harri ;

Blom, Tea ;

Maenpaa, Hanna ;

Isola, Jorma ;

Paetau, Anders ;

Joensuu, Heikki ;

Nupponen, Nina N. .

MOLECULAR CANCER RESEARCH, 2006, 4 (12) :927-934

[17] Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development [J].

Stephens, Philip J. ;

Greenman, Chris D. ;

Fu, Beiyuan ;

Yang, Fengtang ;

Bignell, Graham R. ;

Mudie, Laura J. ;

Pleasance, Erin D. ;

Lau, King Wai ;

Beare, David ;

Stebbings, Lucy A. ;

McLaren, Stuart ;

Lin, Meng-Lay ;

McBride, David J. ;

Varela, Ignacio ;

Nik-Zainal, Serena ;

Leroy, Catherine ;

Jia, Mingming ;

Menzies, Andrew ;

Butler, Adam P. ;

Teague, Jon W. ;

Quail, Michael A. ;

Burton, John ;

Swerdlow, Harold ;

Carter, Nigel P. ;

Morsberger, Laura A. ;

Iacobuzio-Donahue, Christine ;

Follows, George A. ;

Green, Anthony R. ;

Flanagan, Adrienne M. ;

Stratton, Michael R. ;

Futreal, P. Andrew ;

Campbell, Peter J. .

CELL, 2011, 144 (01) :27-40

[18] Genetic alterations and in vivo tumorigenicity of neurospheres derived from an adult glioblastoma [J].

Tunici, Patrizia ;

Bissola, Lorena ;

Lualdi, Elena ;

Pollo, Bianca ;

Cajola, Laura ;

Broggi, Giovanni ;

Sozzi, Gabriella ;

Finocchiaro, Gaetano .

MOLECULAR CANCER, 2004, 3 (1)

[19] AMPLIFIED MET GENE LINKED TO DOUBLE MINUTES IN HUMAN GLIOBLASTOMA [J].

WULLICH, B ;

MULLER, HW ;

FISCHER, U ;

ZANG, KD ;

MEESE, E .

EUROPEAN JOURNAL OF CANCER, 1993, 29A (14) :1991-1995

[20] Distant metastasis occurs late during the genetic evolution of pancreatic cancer [J].

Yachida, Shinichi ;

Jones, Sian ;

Bozic, Ivana ;

Antal, Tibor ;

Leary, Rebecca ;

Fu, Baojin ;

Kamiyama, Mihoko ;

Hruban, Ralph H. ;

Eshleman, James R. ;

Nowak, Martin A. ;

Velculescu, Victor E. ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Iacobuzio-Donahue, Christine A. .

NATURE, 2010, 467 (7319) :1114-U126

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