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• W2467392015 abstract "Genomic analyses of low-grade glioma (LGG) are leading to diagnostic and prognostic classification according to IDH mutation and 1p/19q co-deletion status, with patients harboring both alterations enjoying the best prognosis and those whose tumors are driven by other genomic aberrations having survival more comparable to glioblastoma (GBM). We previously used The Cancer Genome Atlas (TCGA) GBM expression profile database to identify a 12-gene set prognostic for survival in GBM. This study aimed to determine whether this gene expression profile may also distinguish favorable and unfavorable subgroups in LGG. Publicly available clinical and gene expression data from 459 grade 2 or 3 astrocytoma, oligodendroglioma, and mixed oligoastrocytoma samples were downloaded from the TCGA data portal. Gene expression data were log2 transformed and used to calculate a meta-gene score, utilizing weighting coefficients derived in our previous modeling of GBM survival (IJROBP 90(1):S38-S39, 2014). Copy number SNP array data were used to assess for 1p/19q co-deletion and sequencing data were used to identify patients with IDH mutations. For survival analysis, patients were stratified into 3 molecular subclasses according to IDH mutation and 1p/19q co-deletion status (IDH mutant + 1p/19q co-deleted; IDH mutant + 1p/19q intact; IDH wild-type), and into favorable (lowest 25%) and unfavorable (highest 75%) meta-gene score groups. Among all patients with LGG, median OS differed significantly between patients with favorable versus unfavorable meta-gene scores based on our 12-gene set (7.3 vs. 10.9 yrs, P = 0.04). The meta-gene score retained prognostic significance in a Cox regression model with age and histopathologic tumor grade as covariates (P = .0005), but fell out of the model when the molecular subclass was entered. The meta-gene score was not associated with survival within IDH-mutant LGG, but trended towards significance within IDH wild-type LGG (P = .14, n = 86). Of 86 IDH wild-type LGGs in the TCGA database, 77 (89.5%) had unfavorable meta-gene scores. Of these 77 patients, 34 (44%) died during follow-up, while only 1 of 9 patients (11%) with IDH wild-type LGG and a favorable meta-gene score died in available follow-up. A 12-gene expression signature derived from analysis of the TCGA GBM database was also found to have prognostic value among lower grade gliomas. IDH wild-type patients were more likely to have unfavorable meta-gene scores, consistent with the hypothesis that IDH wild-type LGG may behave more similarly to GBM than other molecular subclasses. As in GBM, unfavorable meta-gene scores were associated with poor clinical outcomes in IDH wild-type LGG." @default.
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• W2467392015 date "2015-11-01" @default.
• W2467392015 modified "2023-09-27" @default.
• W2467392015 title "Evaluation of the Prognostic Performance of a 12-gene Glioblastoma Signature Among Low-Grade Glioma Patients in the Cancer Genome Atlas Database" @default.
• W2467392015 doi "https://doi.org/10.1016/j.ijrobp.2015.07.333" @default.
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