Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

1.2 Glioblastoma Multiforme Introduction
tumours [154,301,383]. As the moniker "multiforme" implies, GBM is charac-
terised by a widespread intratumoural heterogeneity that makes it extremely
hard to understand and treat [154,383]. The histopathological features of GBM
include nuclear atypia, cellular pleomorphism, mitotic activity, vascular throm-
bosis, microvascular proliferation and necrosis [154,301]. This complexity, com-
bined with a putative cancer stem cell subpopulation and an incomplete atlas
of epigenetic and genetic lesions, has contributed to make this cancer one of
the most difficult to understand and to treat [154].
The average life expectancy of a patient with glioblastoma lies between several
weeks and several months after postoperative radiotherapy, with a protracted
course when treated with temozolomide in addition to radiotherapy alone (Fig
1.1). Median survival is generally less than one year from the time of diag-
nosis and most patients die within two years, with most long-term survivors
being given the wrong histological diagnosis at first [128,472]. Unless the
neoplasm has developed from a lower grade astrocytoma, in more than 50%
of cases the clinical history is less than 3 months. In most European and
North American countries, the incidence lies in the range of 3-4 new cases per
100,000 population per year, preferentially affecting adults and with a slightly
higher incidence in men than women [128,301]. Although infiltrative spread
Figure 1.1: Estimates of survival amongst GBM patients treated with radiotherapy
alone or radiotherapy with the alkylating agent temozolomide. Taken from Stupp et
al 2005 [472].
is a common feature of all diffuse astrocytic tumours, glioblastoma is particu-
larly notorious for its rapid invasion of the neighboring brain structures [154].
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