TP53 Combined Phenotype Score Is Associated with the Clinical Outcome of TP53-Mutated Myelodysplastic Syndromes

Mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the TP53 allelic state and variant allele frequency of TP53 mutation impact patient...

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Autores principales:	Mariko Yabe, Aidana Z. Omarbekova, Meier Hsu, Hannah May, Maria E. Arcila, Ying Liu, Ahmet Dogan, Andrew M. Brunner, Valentina Nardi, Robert P. Hasserjian, Virginia M. Klimek
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	myelodysplastic syndromes <i>TP53</i> prognosis overall survival PHANTM combined phenotype score Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1124622ac9fd44089ab464063b652144
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spelling	oai:doaj.org-article:1124622ac9fd44089ab464063b6521442021-11-11T15:33:45Z<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes10.3390/cancers132155022072-6694https://doaj.org/article/1124622ac9fd44089ab464063b6521442021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5502https://doaj.org/toc/2072-6694Mutations of <i>TP53</i> are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the <i>TP53</i> allelic state and variant allele frequency of <i>TP53</i> mutation impact patient outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with <i>TP53</i>-mutated MDS. We assessed each mutation according to the phenotypic annotation of <i>TP53</i> mutations (PHANTM) and analyzed the associations between predicted <i>TP53</i> mutant function, represented by the PHANTM combined phenotype score, and overall survival (OS) using the log rank test and Cox regression. Our results indicated that patients with PHANTM combined phenotype score above the median (>1) had significantly shorter OS compared to those with scores below the median (median OS: 10.59 and 16.51 months, respectively, <i>p</i> = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), <i>p</i> = 0.044) and identified to have an independent prognostic influence, accounting for known risk such as IPSS-R and other standard risk variables. Our results suggest that the functional information of <i>TP53</i> mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with <i>TP53</i>-mutated MDS.Mariko YabeAidana Z. OmarbekovaMeier HsuHannah MayMaria E. ArcilaYing LiuAhmet DoganAndrew M. BrunnerValentina NardiRobert P. HasserjianVirginia M. KlimekMDPI AGarticlemyelodysplastic syndromes<i>TP53</i>prognosisoverall survivalPHANTM combined phenotype scoreNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5502, p 5502 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	myelodysplastic syndromes <i>TP53</i> prognosis overall survival PHANTM combined phenotype score Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	myelodysplastic syndromes <i>TP53</i> prognosis overall survival PHANTM combined phenotype score Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mariko Yabe Aidana Z. Omarbekova Meier Hsu Hannah May Maria E. Arcila Ying Liu Ahmet Dogan Andrew M. Brunner Valentina Nardi Robert P. Hasserjian Virginia M. Klimek <i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
description	Mutations of <i>TP53</i> are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the <i>TP53</i> allelic state and variant allele frequency of <i>TP53</i> mutation impact patient outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with <i>TP53</i>-mutated MDS. We assessed each mutation according to the phenotypic annotation of <i>TP53</i> mutations (PHANTM) and analyzed the associations between predicted <i>TP53</i> mutant function, represented by the PHANTM combined phenotype score, and overall survival (OS) using the log rank test and Cox regression. Our results indicated that patients with PHANTM combined phenotype score above the median (>1) had significantly shorter OS compared to those with scores below the median (median OS: 10.59 and 16.51 months, respectively, <i>p</i> = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), <i>p</i> = 0.044) and identified to have an independent prognostic influence, accounting for known risk such as IPSS-R and other standard risk variables. Our results suggest that the functional information of <i>TP53</i> mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with <i>TP53</i>-mutated MDS.
format	article
author	Mariko Yabe Aidana Z. Omarbekova Meier Hsu Hannah May Maria E. Arcila Ying Liu Ahmet Dogan Andrew M. Brunner Valentina Nardi Robert P. Hasserjian Virginia M. Klimek
author_facet	Mariko Yabe Aidana Z. Omarbekova Meier Hsu Hannah May Maria E. Arcila Ying Liu Ahmet Dogan Andrew M. Brunner Valentina Nardi Robert P. Hasserjian Virginia M. Klimek
author_sort	Mariko Yabe
title	<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
title_short	<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
title_full	<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
title_fullStr	<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
title_full_unstemmed	<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes
title_sort	<i>tp53</i> combined phenotype score is associated with the clinical outcome of <i>tp53</i>-mutated myelodysplastic syndromes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1124622ac9fd44089ab464063b652144
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<i>TP53</i> Combined Phenotype Score Is Associated with the Clinical Outcome of <i>TP53</i>-Mutated Myelodysplastic Syndromes

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