Molecular characterization of gliosarcoma reveals prognostic biomarkers and clinical parallels with glioblastoma.
CDKN2A/B
LRP1B
TSC2
Molecular profiling
Prognostic marker
Project GENIE
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
16
09
2024
accepted:
18
10
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
aheadofprint
Résumé
Gliosarcoma is a rare histopathological variant of glioblastoma, but it is unclear whether distinct clinical or molecular features distinguish it from other glioblastomas. The purpose of this study was to characterize common genomic alterations of gliosarcoma, compare them to that of glioblastoma, and correlate them with prognosis. This was a single-institution, retrospective cohort study of patients seen between 11/1/2017 to 1/28/2024. Clinical and genomic data were obtained from the medical record. Results were validated using data from AACR Project GENIE (v15.1-public). We identified 87 gliosarcoma patients in the institutional cohort. Compared to a contemporary cohort of 492 glioblastoma, there was no difference in overall survival, though progression free survival was inferior for patients with gliosarcoma (p = 0.01). Several of the most-commonly altered genes in gliosarcoma were more frequently altered than in glioblastoma (NF1, PTEN, TP53), while others were less frequently altered than in glioblastoma (EGFR). CDKN2A/CDKN2B/MTAP alterations were associated with inferior survival on univariate Cox (HR = 5.4, p = 0.023). When pooled with 93 patients from the GENIE cohort, CDKN2A/B (HR = 1.75, p = 0.039), RB1 (HR = 0.51, p = 0.016), LRP1B (p = 0.050, HR = 2.0), and TSC2 (HR = 0.31, p = 0.048) alterations or loss were significantly associated with survival. These effects remained when controlled for age, sex, and cohort of origin with multivariate Cox. Gliosarcoma has a similar overall survival but worse response to treatment and different mutational profile than glioblastoma. CDKN2A/B loss and LRP1B alterations were associated with inferior prognosis, while RB1 or TSC2 alterations were associated with improved outcomes. These findings may have implications for clinical management and therapeutic selection in this patient population.
Identifiants
pubmed: 39476147
doi: 10.1007/s11060-024-04859-0
pii: 10.1007/s11060-024-04859-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Center Core Grant of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ID : NCI P30 CA006973
Organisme : Cancer Center Core Grant of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ID : NCI P30 CA006973
Organisme : Department of Defense
ID : W81XWH-21-1-0251
Informations de copyright
© 2024. The Author(s).
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