Stem cell research points the way to the cell of origin for intracranial germ cell tumours

• Published in: The Journal of pathology 2013-01, Vol.229 (1), p.4-11
• Main Authors: Tan, Chris, Scotting, Paul J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; brain; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Lineage - genetics; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; germ cell tumours; Humans; induced pluripotency; Induced Pluripotent Stem Cells - metabolism; Induced Pluripotent Stem Cells - pathology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Neoplasms, Germ Cell and Embryonal - genetics; Neoplasms, Germ Cell and Embryonal - metabolism; Neoplasms, Germ Cell and Embryonal - pathology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; neural stem cells; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - pathology; Stem Cell Research; teratoma
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.4098

Germ cell tumours found in the brain (intracranial GCTs) are a very unusual class of tumour for two reasons. First, they include a very diverse range of histological subtypes classified together due to their proposed common cell of origin. Second, this proposed cell of origin, the germ cell progenitor, would not normally be found in the tissue where these tumours arise. This is in contrast to all other primary brain tumours, in which the cell of origin is believed to be a brain cell. Indeed, no other class of primary cancer arises from a cell from a distant organ. This theory for the origins of intracranial GCTs has been in place for many decades, but recent data arising from studies of induced pluripotency for regenerative medicine raise serious questions about this dogma. Here we review the cellular origins of intracranial GCTs in the light of these new data and reanalyse the existing data on the biology of this unusual class of tumours. Together, these considerations lead us to conclude that the evidence now falls in favour of a model in which these tumours arise from the transformation of endogenous brain cells. This theory should inform future studies of the aetiology of these tumours and so lead the way to animal models in which to study their development and potential biological therapeutics. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.