Landscape of Genomic Alterations in IDH Wild-Type Glioblastoma Identifies PI3K as a Favorable Prognostic Factor.
JCO Precis Oncol
; 4: 575-584, 2020 Nov.
Article
en En
| MEDLINE
| ID: mdl-35050747
ABSTRACT
PURPOSE:
IDH wild-type (WT) glioblastoma (GBM) is an aggressive tumor with poor survival despite current therapies. The aim of this study was to characterize its genomic profile and determine whether a particular molecular signature is associated with improved survival outcomes. PATIENTS ANDMETHODS:
Tumor samples from 232 patients with IDH-WT GBM were sequenced, and the landscape of genomic alterations was fully delineated. Genomics data from The Cancer Genome Atlas (TCGA) cohort were analyzed for confirmation. Association of alterations with survival was evaluated in both univariable and multivariable approaches.RESULTS:
The genomic landscape of IDH-WT GBM revealed a high frequency of CDKN2A/B loss, TERT promoter mutations, PTEN loss, EGFR alteration, and TP53 mutations. Novel variants or gene mutations, such as ARID1B and MLL2, were identified. To better understand synergistic effects and facilitate decision making for precision medicine, we identified 11 pairs of gene alterations that tended to co-occur or were mutually exclusive, which were confirmed in the TCGA cohort. Survival analysis showed that genomic alterations in TP53 were associated with worse overall survival (OS). However, alterations in PI3K class I genes were associated with significantly better OS (univariableanalysis:
P = .002; multivariableanalysis:
hazard ratio [HR], 0.5785; P = .00162) and longer progression-free survival (univariableanalysis:
P = .0043; multivariableanalysis:
HR, 0.6228; P = .00913).CONCLUSION:
Genomic alterations in PI3K class I are a favorable prognostic factor in IDH-WT GBM. This new prognostic biomarker may facilitate risk stratification of patients, assist in clinical trial enrollment, and provide potential therapeutic targets.
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Bases de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
JCO Precis Oncol
Año:
2020
Tipo del documento:
Article