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Origins of brain tumors—a disease of stem cells?

Nature Clinical Practice Neurology volume 2, pages 288–289 (2006)Cite this article

Brain cancer is one of the most devastating CNS pathologies. The majority of adult CNS tumors are glial and classified as astrocytic, oligodendrocytic or mixed on the basis of gene expression and morphologic similarities to normal cells of the respective cell type. Gliomas either present as high-grade tumors, or progress towards a higher grade and more undifferentiated character as tumor cells acquire additional mutations over time. Patients with lower grade gliomas often survive for many years, but people with infiltrating grade IV astrocytic neoplasm glioblastoma multiforme have a median survival of approximately 1 year.1

Brain tumor cells display various stem-like characteristics, such as the ability to proliferate indefinitely, form tumors on transplantation and accumulate mutations owing to self-perpetuation, which raises questions of stem-cell involvement in disease etiology.2 The adult brain, largely composed of highly specialized differentiated cell types, also contains undifferentiated multipotent and self-renewing neural stem cells (NSCs) that could in principle acquire mutations and become transformed.3,4 These neural stem/progenitor cells located in areas of adult neurogenesis, such as the hippocampus, subventricular zone and olfactory bulbs, are normally quiescent, but can be induced to proliferate under conditions of stress.4 In addition, signaling abnormalities frequently found in brain tumors occur in pathways involving/activated by proteins encoded by genes that have been implicated in the regulation of stem-cell proliferation and self-renewal (e.g. EGF [epidermal growth factor], PTEN, Myc, Shh [sonic hedgehog] or Notch).2,3,4 Moreover, brain tumors contain heterogeneous cell populations with regard to the expression of stage-specific differentiation markers, and this heterogeneity has often been compared to the variety of cell types of the NSC lineage observed during normal brain development.3,4

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Authors and Affiliations

  1. Department of Cancer Biology and Genetics at Weill Cornell Graduate School of Medical Sciences,

    Elena I Fomchenko & Eric C Holland

  2. professor of cancer biology/genetics and an attending professor of neurosurgery/neurology at Memorial Sloan–Kettering Cancer Center, New York, NY, USA

    Elena I Fomchenko & Eric C Holland

Authors
  1. Elena I Fomchenko
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  2. Eric C Holland
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Correspondence to Eric C Holland.

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Fomchenko, E., Holland, E. Origins of brain tumors—a disease of stem cells?. Nat Rev Neurol 2, 288–289 (2006). https://doi.org/10.1038/ncpneuro0200

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