Mismigrating germ-cell progenitors have historically been accepted as the cell of origin for central nervous system (CNS)
germinomas. However, an alternative hypothesis suggests that CNS
germinomas arise from a brain-cell progenitor.
Germinomas often acquire Kit signaling pathway mutations, and there is evidence for an oncogenic relationship between KIT and the ETV1
transcription factor. KIT appears to be necessary to stabilize ETV1, and ETV1 then activates
oncogenesis-associated genes. ETV1 expression is not increased by KIT, so ETV1 already needs to be expressed in order for KIT to have an oncogenic function. Therefore, if brain-cell progenitors are the cell of origin for
germinomas, those cells would already need to coexpress ETV1 and KIT. We examined Kit and Etv1 in situ hybridization data from the Allen Brain Atlas, for mouse brain tissue at various stages of development. Both Kit and Etv1 were expressed in the regions where
germinomas most commonly arise, and in the medulla oblongata. All human cases of
germinomas correlated to the regions where ETV1 and KIT are coexpressed. We therefore postulate that
germinomas in the brain share a similar mechanism with other KIT-driven
cancers, which supports the hypothesis that
germinomas arise from a brain-cell progenitor.