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Review

Neuro-oncogenesis and the adult human sub-

ventricular zone in high grade glioma

Sara G. M. Piccirillo
John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0PY, UK.

Dr. Sara G. M. Piccirillo graduated from the University of Milan in Medical Biotechnology in 2003 and gained her
Ph.D. in Translational and Molecular Medicine at the University of Milan-Bicocca in 2008. Dr. Piccirillo is currently
the Research Associate at the Department of Clinical Neurosciences of Cambridge University in UK. Since 2014, she is
also the Visiting Senior Scientist at the University of Texas Southwestern Medical Center in Dallas in USA.

A B S T R AC T
The last fifteen years have seen the application of the cancer stem cell hypothesis to tumors of the central nervous system, in
particular to high grade glioma (HGG), the most aggressive and common brain cancer in adults. Seminal studies have shown
that cancer stem cells (alternatively named tumor-initiating cells) are capable of self-renew and multipotency, similar to their
normal counterpart. More importantly they give rise to tumors that closely mimic the phenotype and genotype of human HGG.
The identification of neurogenic niches in adult rodent and human brain has further reinforced the hypothesis that HGG might
derive from the malignant transformation occurring in these areas, especially in the sub-ventricular zone (SVZ), the largest and
most well characterised stem cell niche. Following from evidence of animal model studies supporting this hypothesis, recently
we investigated the role of the SVZ in neuro-oncogenesis using tissue material derived from HGG patients. We also described
response to conventional chemo-therapies of cancer stem cells isolated from the SVZ and the tumor mass (T) of the same patients
and reconstructed tumor evolution. In this review, such findings will be discussed in the context of the current literature on the
biology of the SVZ in the normal and disease brain.

Key words: High grade glioma; tumor-initiating cells; sub-ventricular zone; tumor development

INTRODUCTION tumors and secondly, the application of high-resolution
genomics to study HGG genetic heterogeneity. However,
High grade glioma (HGG) are aggressive and lethal the existence of cancer stem cells in tumors does not
brain tumors whose prognosis remains dismal despite prove per se that the disease originates from normal
advances in neurosurgical techniques and combination stem cells.
of radio- and chemo-therapy. The recent years have
seen two major directions of investigation: firstly, the In the brain, the sub-ventricular zone (SVZ) is a
evidence from stem cell biology showing that cancer germinal niche where neurogenesis persists throughout
stem-like populations exist in HGG and other brain adulthood. In the last twenty years, seminal studies
have described the cellular organisation and functional
Corresponding Author: Dr. Sara G. M. Piccirillo, John properties of this niche, mainly composed of neural
van Geest Centre for Brain Repair, Department of Clinical stem, precursor cells and migrating neuroblasts. Given
Neurosciences, University of Cambridge, Cambridge, CB2 0PY,
UK. E-mail: sara.piccirillo@gmail.com
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Cite this article as: Piccirillo SGM. Neuro-oncogenesis and the adult
DOI: human sub-ventricular zone in high grade glioma. Neuroimmunol
10.20517/2347-8659.2015.37 Neuroinflammation 2016;3:20-6.
Received: 15-09-2015; Accepted: 30-11-2015

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