authors demonstrate that multiple normal cell
types within the central nervous system can
be transformed into tumors, consistent with
findings that multiple hematopoietic cells
types can be transformed in leukemia development
( 7, 8). However, which hematopoietic
cell types can be transformed is determined
by the initiating oncogene, demonstrating an
interaction between the epigenetic state of the
cell of origin and the initiating oncogene ( 9,
10). The study by Friedmann-Morvinski et al.
indicates that both neuronal and glial cells,
upon loss of the tumor suppressor proteins
p53 and neurofi bromatosis–1 (NF1), reactivated
expression of markers normally found
in immature cells of the nervous system. The
transformed cells expressing the immature
markers then gave rise to tumors. Therefore,
cancer cells may not follow the same strict
relationships and directionality that normal
cells follow during lineage development.
The fi nding of Friedmann-Morvinski et
al. does not rule out a hierarchical relationship
between cells in a fully developed cancer,
with some cells being more tumorigenic than
others. However, if more differentiated cells
can be transformed and revert to more immature
states, markers of normal differentiation
will not consistently identify the most tumorigenic
populations. Indeed, mouse models of