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Article

TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy

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Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2031, Australia
2
Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Randwick, NSW 2031, Australia
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Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2031, Australia
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Translational Cancer Metabolism Laboratory, School of Medical Sciences, Prince of Wales Clinical School, UNSW Sydney, Sydney, NSW 2031, Australia
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School of Women’s & Children’s Health, UNSW Medicine, University of NSW, Randwick, NSW 2031, Australia
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Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Randwick, NSW 2031, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Eiichi Ishikawa
Cancers 2021, 13(21), 5362; https://doi.org/10.3390/cancers13215362
Received: 9 September 2021 / Revised: 17 October 2021 / Accepted: 22 October 2021 / Published: 26 October 2021
Molecular biomarkers are utilised for the development of targeted therapy and diagnostic or prognostic tools and in strategising therapeutic approaches as they may have an effect in drug response. In lower-grade glioma (LGG), there are currently no established biomarkers that are associated with chemosensitivity. Here, we identified tumour protein 53 (TP53) hotspot mutations in TP53 codon 273 in 33% (17/51) of astrocytoma tissues and retrospectively found that these tumours were associated with significantly improved clinical outcomes when treated with chemotherapy. We used publicly available datasets to successfully confirm these findings. A potential mechanism of this chemosensitivity was explored in this study. TP53 codon 273 mutations can, thus, potentially be an indicator of chemotherapeutic efficacy in astrocytoma, and it may be useful in making astrocytoma treatment decisions.
Background: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in tumour protein 53 (TP53) is prevalent in astrocytoma, the prognostic effects of TP53 mutation are unclear. Methods: In this retrospective study, we sequenced TP53 exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings. Results: In astrocytoma, mutations in TP53 codon 273 were associated with a significantly increased OS compared to the TP53 wild-type (HR (95% CI): 0.169 (0.036–0.766), p = 0.021). Public datasets confirmed these findings. TP53 codon 273 mutant astrocytomas were significantly more chemosensitive than TP53 wild-type astrocytomas (HR (95% CI): 0.344 (0.13–0.88), p = 0.0148). Post-chemotherapy, a significant correlation between TP53 and YAP1 mRNA was found (p = 0.01). In O (6)-methylguanine methyltransferase (MGMT) unmethylated chemotherapy-treated astrocytoma, both TP53 codon 273 and YAP1 mRNA were significant prognostic markers. In oligodendroglioma, TP53 mutations were associated with significantly decreased OS. Conclusions: Based on these findings, we propose that certain TP53 mutant astrocytomas are chemosensitive through the involvement of YAP1, and we outline a potential mechanism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes. View Full-Text
Keywords: TP53 mutation; low-grade glioma; LGG; MGMT methylation; YAP1; chemosensitivity; temozolomide; prognostic factor; R273H; R273C TP53 mutation; low-grade glioma; LGG; MGMT methylation; YAP1; chemosensitivity; temozolomide; prognostic factor; R273H; R273C
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MDPI and ACS Style

Noor, H.; Briggs, N.E.; McDonald, K.L.; Holst, J.; Vittorio, O. TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy. Cancers 2021, 13, 5362. https://doi.org/10.3390/cancers13215362

AMA Style

Noor H, Briggs NE, McDonald KL, Holst J, Vittorio O. TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy. Cancers. 2021; 13(21):5362. https://doi.org/10.3390/cancers13215362

Chicago/Turabian Style

Noor, Humaira, Nancy E. Briggs, Kerrie L. McDonald, Jeff Holst, and Orazio Vittorio. 2021. "TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy" Cancers 13, no. 21: 5362. https://doi.org/10.3390/cancers13215362

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