Even Cancers Want Commitment: Lineage Identity and Medulloblastoma Formation

Abstract

In this issue of Cancer Cell, Yang et al. (2008) and Schüller et al. (2008) show that Hedgehog activation in either multipotent neural stem cells or developmentally restricted progenitors causes only medulloblastomas to form. These data suggest that some stem cell-derived tumors must commit to a specific lineage in order to grow.

Brain cancer propagating cells: biology, genetics and targeted therapies

“…NSCs are found in different areas of the brain, including around the ventricular system (subventricular zone (SVZ), subependymal zone, lining of the lateral ventricles and cerebellar ventricular zone), dentate gyrus, hippocampus and subcortical white matter [14–16]. During human development, the one important source of NSCs is the SVZ, a region localized between the lateral ventricle and parenchyma of the striatum.…”

“…The cerebellar ventricular zone, which consists of a band of NSCs and PGCs that line the fourth ventricle, gives rise to granule neuron precursors (GNPs) [14]. These are restricted PGCs that can give rise to MB [26].…”

“…These are restricted PGCs that give rise to only granule neurons. The cerebellar ventricular zone, which consists of a band of stem and progenitor cells that line the fourth ventricle, gives rise to the GNPs [14]. The GNPs proliferate in the EGL and then migrate to form the internal granule layer after differentiation to neurons.…”

Erratum: Mitogenic Sonic hedgehog signaling drives E2F1-dependent lipogenesis in progenitor cells and medulloblastoma

“…In development, loss of hedgehog signaling results in severe abnormalities in mice and humans (Chiang et al, 1996). Conversely, unrestrained hedgehog pathway activation is implicated in a variety of tumors, many of which can be traced to hedgehog-dependent progenitors (Beachy et al, 2004;Eberhart, 2008;Teglund and Toftgard, 2010). Tumors associated with Hh aberrations comprise cancers of the skin, pancreas, lung, and the brain cancer medulloblastoma (Teglund and Toftgard, 2010;Wetmore, 2003), the most common solid malignant pediatric tumor, and a leading cause of cancer deaths in children.…”

“…Medulloblastoma arises in the cerebellum as a result of aberrant activity of developmentally critical signaling pathways, including those activated by wnt, Notch, and Shh. Of note, Shh mitogenic signaling is required for normal cerebellum development (Dahmane and Ruiz-i-Altaba, 1999;Wechsler-Reya and Scott, 1999), which is marked by a brief period of rapid proliferation of Cerebellar Granule Neuron Precursor cells (CGNPs), proposed to be cells of origin for certain genetically defined classes of medulloblastoma (Eberhart, 2008).…”