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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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Chapter 9<br />

Discussion<br />

9.1 Digital Pr<strong>of</strong>iling <strong>of</strong> GNS Cell Lines<br />

Gliobastoma multiforme is the most common primary brain tumour and the<br />

most aggressive glioma in adults. No effective solution has been embodied<br />

as a treatment yet, causing the prognosis for this disease to be very poor,<br />

with a median survival time <strong>of</strong> 15 months [472]. The extensive cellular het-<br />

erogeneity typical <strong>of</strong> glioblastomas is confirmed by the consistently different<br />

molecular signatures and copy number variations observed in the subclasses<br />

present within the primary and secondary subtypes [154,334,450]. These ob-<br />

servations are very important since they point at the need for approaching<br />

treatment research from a more molecular standpoint that allows for patient<br />

treatment diversification, in which the patient’s genome is specifically tailored<br />

to obtain the most effective results. An important finding within the cancer<br />

stem cell field in the context <strong>of</strong> glioblastomas, was the observation that these<br />

tumours contain a population <strong>of</strong> cells with similarities to NS cells. Before<br />

then, gliomas were studied as cancer cell lines, which hid the underlying stem<br />

cell component <strong>of</strong> the tumour by causing it to differentiate and could therefore<br />

never be specifically targeted. NS cells give rise to both neurons and glia during<br />

the development <strong>of</strong> the nervous system and are present in restricted regions <strong>of</strong><br />

the adult human brain, where they constitute proliferating germinative zones<br />

that are active throughout adulthood [248]. According to the cancer stem cell<br />

hypothesis, such stem cell-like cell populations are responsible for maintaining<br />

cancers, as well as giving rise to the differentiated progeny responsible for the<br />

cellular diversity <strong>of</strong> many neoplasias, including glioblastoma [379]. If this is<br />

the case, isolating and characterizing the glioma cancer stem cells will be key<br />

to developing efficient therapies for glioblastoma multiforme.<br />

220

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