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Neuro Oncol. 2017 Jun 1;19(6):786-795. doi: 10.1093/neuonc/now285.

Multigene signature for predicting prognosis of patients with 1p19q co-deletion diffuse glioma.

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Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Program of Bioinformatics and Biostatistics, The University of Texas-Houston Graduate School of Biomedical Sciences, Houston, Texas
Jackson Laboratory for Genomic Medicine, Farmington, Connecticut
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas



Co-deletion of 1p and 19q marks a diffuse glioma subtype associated with relatively favorable overall survival; however, heterogeneous clinical outcomes are observed within this category.


We assembled gene expression profiles and sample annotation of 374 glioma patients carrying the 1p/19q co-deletion. We predicted 1p/19q status using gene expression when annotation was missing. A first cohort was randomly split into training (n = 170) and a validation dataset (n = 163). A second validation set consisted of 41 expression profiles. An elastic-net penalized Cox proportional hazards model was applied to build a classifier model through cross-validation within the training dataset.


The selected 35-gene signature was used to identify high-risk and low-risk groups in the validation set, which showed significantly different overall survival (P = .00058, log-rank test). For time-to-death events, the high-risk group predicted by the gene signature yielded a hazard ratio of 1.78 (95% confidence interval, 1.02-3.11). The signature was also significantly associated with clinical outcome in the The Cancer Genome Atlas (CGA) IDH-mutant 1p/19q wild-type and IDH-wild-type glioma cohorts. Pathway analysis suggested that high risk was associated with increased acetylation activity and inflammatory response. Tumor purity was found to be significantly decreased in high-risk IDH-mutant with 1p/19q co-deletion gliomas and IDH-wild-type glioblastomas but not in IDH-wild-type lower grade or IDH-mutant, non-co-deleted gliomas.


We identified a 35-gene signature that identifies high-risk and low-risk categories of 1p/19q positive glioma patients. We have demonstrated heterogeneity amongst a relatively new glioma subtype and provided a stepping stone towards risk stratification.


1p/19q co-deletion; elastic net Cox regression model; glioma; prognostic factor

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