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Acta Neuropathol Commun. 2017 May 22;5(1):39. doi: 10.1186/s40478-017-0443-7.

Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.

Author information

1
Department of Pathology, Division of Neuropathology, University of Washington School of Medicine, 325 9th Avenue, Box 359791, Seattle, WA, 98104, USA. pjjc@uw.edu.
2
Division of Human Biology, and Seattle Tumor and Translational Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Mailstop C3-168, Seattle, WA, 98109, USA. pjjc@uw.edu.
3
Division of Human Biology, and Seattle Tumor and Translational Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Mailstop C3-168, Seattle, WA, 98109, USA.
4
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
5
Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
6
CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
German Cancer Consortium (DKTK), Heidelberg, Germany.
8
Department of Pediatrics, Division of Pediatric Neurooncology, Heidelberg University Hospital, Heidelberg, Germany.
9
Department of Pediatric Immunology, Division of Pediatric Neurooncology, Heidelberg University Hospital, Heidelberg, Germany.
10
Department of Neuropathology, Heinrich Heine University, Duesseldorf, Germany.
11
German Cancer Consortium (DKTK), partner site Essen/Duesseldorf, German Cancer Research Center (DKFZ), Heidelberg, Germany.
12
Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
13
Division of Human Biology, and Seattle Tumor and Translational Research, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Mailstop C3-168, Seattle, WA, 98109, USA. eholland@fredhutch.org.
14
Department of Neurological Surgery, Alvord Brain Tumor Center, University of Washington School of Medicine, Seattle, WA, USA. eholland@fredhutch.org.

Abstract

Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II-IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status. For now, grading of diffuse gliomas is still dependent upon histological parameters. Independent of WHO classification criteria, multidimensional scaling analysis of molecular signatures for diffuse gliomas from The Cancer Genome Atlas (TCGA) has identified distinct molecular subgroups, and allows for their visualization in 2-dimensional (2D) space. Using the web-based platform Oncoscape as a tool, we applied multidimensional scaling-derived molecular groups to the 2D visualization of the 2016 WHO classification of diffuse gliomas. Here we show that molecular multidimensional scaling of TCGA data provides 2D clustering that represents the 2016 WHO classification of diffuse gliomas. Additionally, we used this platform to successfully identify and define novel copy-number alteration-based molecular subtypes, which are independent of WHO grading, as well as predictive of clinical outcome. The prognostic utility of these molecular subtypes was further validated using an independent data set of the German Glioma Network prospective glioblastoma patient cohort.

KEYWORDS:

Astrocytoma; Glioblastoma; Glioma; Isocitrate Dehydrogenase (IDH); Oligodendroglioma; Oncoscape; World Health Organization (WHO)

PMID:
28532485
PMCID:
PMC5439117
DOI:
10.1186/s40478-017-0443-7
[Indexed for MEDLINE]
Free PMC Article

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