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Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma
BACKGROUND: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogen...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390081/ https://www.ncbi.nlm.nih.gov/pubmed/37528810 http://dx.doi.org/10.1093/noajnl/vdad078 |
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author | Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Makino, Ryutaro Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Kirishima, Mari Hamada, Taiji Noguchi, Naoki Otsuji, Ryosuke Kuga, Daisuke Nagasaka, Shohei Yamahata, Hitoshi Yamamoto, Junkoh Yoshimoto, Koji Tanimoto, Akihide Hanaya, Ryosuke |
author_facet | Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Makino, Ryutaro Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Kirishima, Mari Hamada, Taiji Noguchi, Naoki Otsuji, Ryosuke Kuga, Daisuke Nagasaka, Shohei Yamahata, Hitoshi Yamamoto, Junkoh Yoshimoto, Koji Tanimoto, Akihide Hanaya, Ryosuke |
author_sort | Higa, Nayuta |
collection | PubMed |
description | BACKGROUND: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. METHODS: Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. RESULTS: TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan–Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. CONCLUSIONS: Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas. |
format | Online Article Text |
id | pubmed-10390081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103900812023-08-01 Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Makino, Ryutaro Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Kirishima, Mari Hamada, Taiji Noguchi, Naoki Otsuji, Ryosuke Kuga, Daisuke Nagasaka, Shohei Yamahata, Hitoshi Yamamoto, Junkoh Yoshimoto, Koji Tanimoto, Akihide Hanaya, Ryosuke Neurooncol Adv Clinical Investigations BACKGROUND: Telomerase reverse transcriptase promoter (TERTp) mutations are a biological marker of glioblastoma; however, the prognostic significance of TERTp mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase (IDH)- and TERTp-wild-type glioblastomas. METHODS: Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type IDH. RESULTS: TERTp mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were TERTp-wild-type. Among the TERTp-wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without phosphatase and tensin homolog (PTEN) loss and/or mutation. Patients with TERTp-wild-type glioblastomas with PTEN loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without PTEN loss and/or mutation. We divided the patients with TERTp-wild-type into 3 clusters using unsupervised hierarchical clustering: Good (PTEN and TP53 alterations; lack of CDKN2A/B homozygous deletion and platelet-derived growth factor receptor alpha (PDGFRA) alterations), intermediate (PTEN alterations, CDKN2A/B homozygous deletion, lack of PDGFRA, and TP53 alterations), and poor (PDGFRA and TP53 alterations, CDKN2A/B homozygous deletion, and lack of PTEN alterations) outcomes. Kaplan–Meier survival analysis indicated that these clusters significantly correlated with the overall survival of TERTp-wild-type glioblastoma patients. CONCLUSIONS: Here, we report that PTEN loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with IDH- and TERTp-wild-type glioblastomas. The combination of 4 genes, PTEN, TP53, CDKN2A/B, and PDGFRA, is important for the molecular classification and individual prognosis of patients with IDH- and TERTp-wild-type glioblastomas. Oxford University Press 2023-06-28 /pmc/articles/PMC10390081/ /pubmed/37528810 http://dx.doi.org/10.1093/noajnl/vdad078 Text en © The Author(s) 2023. 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 | Clinical Investigations Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Makino, Ryutaro Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Kirishima, Mari Hamada, Taiji Noguchi, Naoki Otsuji, Ryosuke Kuga, Daisuke Nagasaka, Shohei Yamahata, Hitoshi Yamamoto, Junkoh Yoshimoto, Koji Tanimoto, Akihide Hanaya, Ryosuke Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title | Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title_full | Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title_fullStr | Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title_full_unstemmed | Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title_short | Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
title_sort | favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma |
topic | Clinical Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390081/ https://www.ncbi.nlm.nih.gov/pubmed/37528810 http://dx.doi.org/10.1093/noajnl/vdad078 |
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