Towards a lineage-based classification system for gliomas: innovation or imagination?

Recently, developmental neurobiologists have identified multipotential stem cells in the mature nervous systems of vertebrates. The identification of these progenitor cells, which perdure into adulthood, may have important implications for how we think about brain tumor pathology, as we must now consider the possibility that some tumors may arise from these multipotential precursor cells. Currently, neuropathological classification systems are based primarily upon morphological criteria. While these classification systems provide important information regarding prognosis, they have thus far provided little insight into how, from where, and why any given tumor arises. Even prior to having the knowledge that stem cells are present in the adult central nervous system (CNS), several investigators began to explore the idea that antigenic markers, which have proven invaluable to our understanding of what constitutes the normal repertoire of behaviors and lineages of CNS cells, may provide insights into the basic biology of brain tumors. In the following exegesis, we first highlight two papers that review some of the exciting recent advances in developmental neurobiology and point out what implications this may have on our understanding of brain malignancies. We then present several studies in which the investigators sought to test the hypothesis that the antigenic markers that have proved so useful for the developmental neurobiologist may also prove useful in trying to understand the similarities and differences in various categories of brain tumors. While none of these studies demonstrate definitively that brain tumors can or do arise from the aberrant behavior of CNS stem cells, they do provide enough circumstantial evidence that this may be the case to warrant further serious investigation of this hypothesis.