Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes

被引：151

作者：

Jacques, Thomas S. ^{[2
,3
]}

Swales, Alexander ^{[4
]}

Brzozowski, Monika J.

Henriquez, Nico V.

Linehan, Jacqueline M. ^{[4
]}

Mirzadeh, Zaman ^{[5
,6
]}

Malley, Catherine O' ^{[4
]}

Naumann, Heike ^{[4
]}

Alvarez-Buylla, Arturo ^{[5
,6
]}

Brandner, Sebastian ^{[1
]}

机构：

[1] UCL Inst Neurol, Dept Neurodegenerat Dis, Div Neuropathol, London WC1N 3BG, England

[2] UCL Inst Child Hlth, Neural Dev Unit, London, England

[3] Great Ormond St Hosp Sick Children, Dept Histopathol, London, England

[4] UCL Inst Neurol, MRC Pr Unit, London WC1N 3BG, England

[5] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA

来源：

EMBO JOURNAL | 2010年 / 29卷 / 01期

关键词：

brain tumour; soil and seed; stem cells; subventricular zone; tumour suppressor gene; MOUSE MODEL; SUPPRESSOR GENE; CRE RECOMBINASE; GLIOMA; INACTIVATION; ASTROCYTOMA; PTEN; EXPRESSION; P53; PROGENITORS;

D O I：

10.1038/emboj.2009.327

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It has been suggested that intrinsic brain tumours originate from a neural stem/progenitor cell population in the subventricular zone of the post-natal brain. However, the influence of the initial genetic mutation on the phenotype as well as the contribution of mature astrocytes to the formation of brain tumours is still not understood. We deleted Rb/p53, Rb/p53/PTEN or PTEN/p53 in adult subventricular stem cells; in ectopically neurografted stem cells; in mature parenchymal astrocytes and in transplanted astrocytes. We found that only stem cells, but not astrocytes, gave rise to brain tumours, independent of their location. This suggests a cell autonomous mechanism that enables stem cells to generate brain tumours, whereas mature astrocytes do not form brain tumours in adults. Recombination of PTEN/p53 gave rise to gliomas whereas deletion of Rb/p53 or Rb/p53/PTEN generated primitive neuroectodermal tumours (PNET), indicating an important role of an initial Rb loss in driving the PNET phenotype. Our study underlines an important role of stem cells and the relevance of initial genetic mutations in the pathogenesis and phenotype of brain tumours. The EMBO Journal (2010) 29, 222-235. doi: 10.1038/emboj.2009.327; Published online 19 November 2009

引用

页码：222 / 235

页数：14

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