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Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma

BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzi...

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Autores principales: Higa, Nayuta, Akahane, Toshiaki, Yokoyama, Seiya, Yonezawa, Hajime, Uchida, Hiroyuki, Takajo, Tomoko, Otsuji, Ryosuke, Hamada, Taiji, Matsuo, Kei, Kirishima, Mari, Hata, Nobuhiro, Hanaya, Ryosuke, Tanimoto, Akihide, Yoshimoto, Koji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332894/
https://www.ncbi.nlm.nih.gov/pubmed/35911637
http://dx.doi.org/10.1093/noajnl/vdac097
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author Higa, Nayuta
Akahane, Toshiaki
Yokoyama, Seiya
Yonezawa, Hajime
Uchida, Hiroyuki
Takajo, Tomoko
Otsuji, Ryosuke
Hamada, Taiji
Matsuo, Kei
Kirishima, Mari
Hata, Nobuhiro
Hanaya, Ryosuke
Tanimoto, Akihide
Yoshimoto, Koji
author_facet Higa, Nayuta
Akahane, Toshiaki
Yokoyama, Seiya
Yonezawa, Hajime
Uchida, Hiroyuki
Takajo, Tomoko
Otsuji, Ryosuke
Hamada, Taiji
Matsuo, Kei
Kirishima, Mari
Hata, Nobuhiro
Hanaya, Ryosuke
Tanimoto, Akihide
Yoshimoto, Koji
author_sort Higa, Nayuta
collection PubMed
description BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM. METHODS: Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status. RESULTS: We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P < .001). CONCLUSIONS: Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM.
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spelling pubmed-93328942022-07-29 Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Otsuji, Ryosuke Hamada, Taiji Matsuo, Kei Kirishima, Mari Hata, Nobuhiro Hanaya, Ryosuke Tanimoto, Akihide Yoshimoto, Koji Neurooncol Adv Basic and Translational Investigations BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM. METHODS: Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status. RESULTS: We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P < .001). CONCLUSIONS: Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM. Oxford University Press 2022-06-21 /pmc/articles/PMC9332894/ /pubmed/35911637 http://dx.doi.org/10.1093/noajnl/vdac097 Text en © The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic and Translational Investigations
Higa, Nayuta
Akahane, Toshiaki
Yokoyama, Seiya
Yonezawa, Hajime
Uchida, Hiroyuki
Takajo, Tomoko
Otsuji, Ryosuke
Hamada, Taiji
Matsuo, Kei
Kirishima, Mari
Hata, Nobuhiro
Hanaya, Ryosuke
Tanimoto, Akihide
Yoshimoto, Koji
Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title_full Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title_fullStr Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title_full_unstemmed Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title_short Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
title_sort prognostic impact of pdgfra gain/amplification and mgmt promoter methylation status in patients with idh wild-type glioblastoma
topic Basic and Translational Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332894/
https://www.ncbi.nlm.nih.gov/pubmed/35911637
http://dx.doi.org/10.1093/noajnl/vdac097
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