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Genetic
alterations and in vivo tumorigenicity of neurospheres derived from an adult
glioblastoma
Patrizia Tunici1,
Lorena Bissola1, Elena Lualdi2, Bianca
Pollo3, Laura Cajola1, Giovanni Broggi4,
Gabriella Sozzi2 and Gaetano Finocchiaro1
1Istituto Nazionale Neurologico Besta, Dept. Experimental Neurology,
Milano, Italy. 2Istituto Nazionale Tumori, Dept. Experimental
Oncology, Milano, Italy. 3Istituto Nazionale Neurologico Besta, Dept.
Clinical Neurosciences, Milano, Italy. 4Istituto Nazionale
Neurologico Besta, Dept. Neurosurgery; Milano, Italy.
Received: 30 August 2004, Accepted: 6 October 2004, Published:
6 October 2004.
Pediatric brain tumors may originate from cells endowed with
neural stem/precursor cell properties, growing in vitro as neurospheres.
We have
found that these cells can also be present in adult brain tumors and form highly
infiltrating gliomas in the brain of immunodeficient mice.
Neurospheres were
grown from three adult brain tumors and two pediatric gliomas.
Differentiation
of the neurospheres from one adult glioblastoma decreased nestin expression and
increased that of glial and neuronal markers.
Loss of heterozygosity of 10q and
9p was present in the original glioblastoma, in the neurospheres and in tumors
grown into mice, suggesting that PTEN and CDKN2A alterations are key genetic
events in tumor initiating cells with neural precursor properties.
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