Document Type
Journal Article
Publication Date
1-1-2016
Journal
Nature Communications
Volume
7
Inclusive Pages
10.1038/ncomms11185
Abstract
Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M-including H3.2K27M-mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Nikbakht, H., Panditharatna, E., Mikael, L., Li, R., Gayden, T., Siu, A., Packer, R. J., Nazarian, J., & +16 additional authors (2016). Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma.. Nature Communications, 7 (). Retrieved from https://hsrc.himmelfarb.gwu.edu/smhs_neuro_facpubs/288
Peer Reviewed
1
Open Access
1
Supplementary Files
Comments
Reproduced with permission of Macmillan Publishers Ltd. Nature Communications.