Age dependent and cellular origin (stem versus progenitor) of a selected group of spontaneous brain tumors in humans

Abstract

The origin of spontaneous human brain tumors has been recently debated as originating from a stem rather than a progenitor cell. Based on the statistical distribution of a selected group of primary brain tumors, and on the clonality and field theory for cancer growth, we propose as plausible the contribution of progenitor cells in the origin of the most common brain tumors such as, pediatric, mixed (glial and neuronal), and the aggressive glioblastoma multiforme in adults. Operationally, stem cell is defined as having a renewal probability of p=1, a progenitor 0<p<1, and a terminally differentiated cell as p=0. The space-time field location (microenvironment, cell-cell interactions...) and mitotic potential of a cell limits the distinguishability between stem and progenitors, due to the interconvertibility of these states via the process of retrodifferentiation (dedifferentiation). If excessively iterated retrodifferentiation of a mitotically competent cell prompts such a cell to organize programs that are atypical vis-à-vis the standard ones. Regarding specifically malignant cells, aperiodic cycles of dedifferentiation favour emergence of subclonal populations whose anachronistic evolution might become idiosyncratically resistant to therapies previously efficient against the initial tumoral mass. Unfortunately the "ab initio" identification of such subclonal "drifters" is impaired by systematic uncertainties as quali-quantified in appendix.