Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma Journal Article

   

Authors:	Ozawa, T.; Riester, M.; Cheng, Y. K.; Huse, J.; Squatrito, M.; Helmy, K.; Charles, N.; Michor, F.; Holland, E. C.
Article Title:	Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma
Abstract:	To understand the relationships between the non-GCIMP glioblastoma (GBM) subgroups, we performed mathematical modeling to predict the temporal sequence of driver events during tumorigenesis. The most common order of evolutionary events is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes. We then developed a computational methodology to identify drivers of broad copy number changes, identifying PDGFA (chr7) and PTEN (chr10) as driving initial nondisjunction events. These predictions were validated using mouse modeling, showing that PDGFA is sufficient to induce proneural-like gliomas and that additional NF1 loss converts proneural to the mesenchymal subtype. Our findings suggest that most non-GCIMP mesenchymal GBMs arise as, and evolve from, a proneural-like precursor. © 2014 Elsevier Inc.
Journal Title:	Cancer Cell
Volume:	26
Issue:	2
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2014-08-11
Start Page:	288
End Page:	300
Language:	English
DOI:	10.1016/j.ccr.2014.06.005
PROVIDER:	scopus
PMCID:	PMC4143139
PUBMED:	25117714
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84905675587&partnerID=40&md5=2c977d149a63403cce88adb7d4f7f400
Notes:	Cited By (since 1996):1 -- Export Date: 2 September 2014 -- CODEN: CCAEC -- Source: Scopus

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