@article{a3381c096d244912af6fc8c218e3c674,
title = "Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma",
abstract = "Summary Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.",
author = "Michele Ceccarelli and Barthel, {Floris P.} and Malta, {Tathiane M.} and Sabedot, {Thais S.} and Salama, {Sofie R.} and Murray, {Bradley A.} and Olena Morozova and Yulia Newton and Amie Radenbaugh and Pagnotta, {Stefano M.} and Samreen Anjum and Jiguang Wang and Ganiraju Manyam and Pietro Zoppoli and Shiyun Ling and Rao, {Arjun A.} and Mia Grifford and Cherniack, {Andrew D.} and Hailei Zhang and Laila Poisson and Carlotti, {Carlos Gilberto} and Tirapelli, {Daniela Pretti Da Cunha} and Arvind Rao and Tom Mikkelsen and Lau, {Ching C.} and Yung, {W. K.Alfred} and Raul Rabadan and Jason Huse and Brat, {Daniel J.} and Lehman, {Norman L.} and Barnholtz-Sloan, {Jill S.} and Siyuan Zheng and Kenneth Hess and Ganesh Rao and Matthew Meyerson and Rameen Beroukhim and Lee Cooper and Rehan Akbani and Margaret Wrensch and David Haussler and Aldape, {Kenneth D.} and Laird, {Peter W.} and Gutmann, {David H.} and Houtan Noushmehr and Antonio Iavarone and Verhaak, {Roel G.W.} and {TCGA Research Network}",
note = "Funding Information: This study was supported by NIH grants U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843, P30CA016672, P50 CA127001, U54CA193313, R01CA179044, R01CA185486, R01 CA190121, and P01 CA085878; Cancer Prevention & Research Institute of Texas (CPRIT) R140606; and S{\~a}o Paulo Research Foundation (FAPESP) 2014/02245-3, 2015/07925-5, 2015/02844-7, and 2015/08321-3. D.J.W. is a consultant for Zymo Research Corporation. R.B. is a consultant for and received grant funding from Novartis. A.D.C. and M.M. received grant support from Bayer. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jan,
day = "28",
doi = "10.1016/j.cell.2015.12.028",
language = "English (US)",
volume = "164",
pages = "550--563",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}
