Multigene signature for predicting prognosis of patients with 1p19q co-deletion diffuse glioma.
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.
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
Xin
X
Hu
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Emmanuel
E
Martinez-Ledesma
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Siyuan
S
Zheng
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas|Jackson Laboratory for Genomic Medicine, Farmington, Connecticut
Hoon
H
Kim
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas|Jackson Laboratory for Genomic Medicine, Farmington, Connecticut
Floris
F
Barthel
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Tao
T
Jiang
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
Kenneth R
KR
Hess
Department of Genomic Medicine, 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|Jackson Laboratory for Genomic Medicine, Farmington, Connecticut
Roel G W
RGW
Verhaak
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D015996:Survival Rate; D059467:Transcriptome; D055815:Young Adult
D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase
1p/19q co-deletion; elastic net Cox regression model; glioma; prognostic factor