Cooperativity within and among Pten, p53, and Rb Pathways Induces High-Grade Astrocytoma in Adult Brain

被引：214

作者：

Chow, Lionel M. L. ^{[1
,5
]}

Endersby, Raelene ^{[1
]}

Zhu, Xiaoyan ^{[1
]}

Rankin, Sherri ^{[1
]}

Qu, Chunxu ^{[2
]}

Zhang, Junyuan ^{[1
]}

Broniscer, Alberto ^{[3
]}

Ellison, David W. ^{[4
]}

Baker, Suzanne J. ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA

[3] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[4] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[5] Cincinnati Childrens Hosp Med Ctr, Dept Hematol Oncol, Cincinnati, OH 45229 USA

来源：

CANCER CELL | 2011年 / 19卷 / 03期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

NEURAL STEM/PROGENITOR CELLS; INTEGRATED GENOMIC ANALYSIS; STEM-CELL; DISEASE PROGRESSION; MOUSE MODEL; SOMA SIZE; EXPRESSION; GLIOMA; DELETION; DEFECTS;

D O I：

10.1016/j.ccr.2011.01.039

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutations in the PTEN, TP53, and RB1 pathways are obligate events in the pathogenesis of human glioblastomas. We induced various combinations of deletions in these tumor suppressors in astrocytes and neural precursors in mature mice, resulting in astrocytomas ranging from grade III to grade IV (glioblastoma). There was selection for mutation of multiple genes within a pathway, shown by somatic amplifications of genes in the PI3K or Rb pathway in tumors in which Pten or Rb deletion was an initiating event. Despite multiple mutations within PI3K and Rb pathways, elevated Mapk activation was not consistent. Gene expression profiling revealed striking similarities to subclasses of human diffuse astrocytoma. Astrocytomas were found within and outside of proliferative niches in the adult brain.

引用

页码：305 / 316

页数：12

共 48 条

[1] Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease [J].

Backman, SA ;

Stambolic, V ;

Suzuki, A ;

Haight, J ;

Elia, A ;

Pretorius, J ;

Tsao, MS ;

Shannon, P ;

Bolon, B ;

Ivy, GO ;

Mak, TW .

NATURE GENETICS, 2001, 29 (04) :396-403

[2] THE NEUROEPITHELIAL STEM-CELL CONCEPT - IMPLICATIONS FOR NEUROONCOLOGY [J].

BRUSTLE, O ;

MCKAY, RDG .

JOURNAL OF NEURO-ONCOLOGY, 1995, 24 (01) :57-59

[3]

Büschges R, 1999, BRAIN PATHOL, V9, P435

[4] Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancer [J].

Cengiz, Beyhan ;

Gunduz, Mehmet ;

Nagatsuka, Hitoshi ;

Beder, Levent ;

Gunduz, Esra ;

Tarnarnura, Ryo ;

Mahmut, Naila ;

Fukushirna, Kunihiro ;

Ali, Mahmoud Al Sheikh ;

NaoMoto, Yoshio ;

Shimizu, Kenji ;

Nagai, Noriyuki .

ORAL ONCOLOGY, 2007, 43 (03) :241-247

[5] Automated Network Analysis Identifies Core Pathways in Glioblastoma [J].

Cerami, Ethan ;

Demir, Emek ;

Schultz, Nikolaus ;

Taylor, Barry S. ;

Sander, Chris .

PLOS ONE, 2010, 5 (02)

[6] Cell type specificity of PI3K signaling in Pdk1-and Pten-deficient brains [J].

Chalhoub, Nader ;

Zhu, Guo ;

Zhu, Xiaoyan ;

Baker, Suzanne J. .

GENES & DEVELOPMENT, 2009, 23 (14) :1619-1624

[7] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[8] Inducible Cre recombinase activity in mouse mature astrocytes and adult neural precursor cells [J].

Chow, Lionel M. L. ;

Zhang, Junyuan ;

Baker, Suzanne J. .

TRANSGENIC RESEARCH, 2008, 17 (05) :919-928

[9] Astrocytes Reverted to a Neural Progenitor-like State with Transforming Growth Factor Alpha Are Sensitized to Cancerous Transformation [J].

Dufour, Christelle ;

Cadusseau, Josette ;

Varlet, Pascale ;

Surena, Anne-Laure ;

de Faria, Giselle P. ;

Dias-Morais, Amelie ;

Auger, Nathalie ;

Leonard, Nadine ;

Daudigeos, Estelle ;

Dantas-Barbosa, Carmela ;

Grill, Jacques ;

Lazar, Vladimir ;

Dessen, Philippe ;

Vassal, Gilles ;

Prevot, Vincent ;

Sharif, Ariane ;

Chneiweiss, Herve ;

Junier, Marie-Pierre .

STEM CELLS, 2009, 27 (10) :2373-2382

[10] Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development [J].

Ferguson, KL ;

Vanderluit, JL ;

Hébert, JM ;

McIntosh, WC ;

Tibbo, E ;

MacLaurin, JG ;

Park, DS ;

Wallace, VA ;

Vooijs, M ;

McConnell, SK ;

Slack, RS .

EMBO JOURNAL, 2002, 21 (13) :3337-3346

← 1 2 3 4 5 →