TP53 combined phenotype score is associated with the clinical outcome of TP53-mutated myelodysplastic syndromes Journal Article
| Authors: | Yabe, M.; Omarbekova, A. Z.; Hsu, M.; May, H.; Arcila, M. E.; Liu, Y.; Dogan, A.; Brunner, A. M.; Nardi, V.; Hasserjian, R. P.; Klimek, V. M. |
| Article Title: | TP53 combined phenotype score is associated with the clinical outcome of TP53-mutated myelodysplastic syndromes |
| Abstract: | 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 outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with TP53-mutated MDS. We assessed each mutation according to the phenotypic annotation of TP53 mutations (PHANTM) and analyzed the associations between predicted TP53 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, p = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), p = 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 TP53 mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with TP53-mutated MDS. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | adult; aged; middle aged; young adult; gene mutation; major clinical study; overall survival; phenotype; neutrophil count; gene frequency; hemoglobin; stem cell transplantation; medical record review; retrospective study; protein p53; prediction; risk assessment; tumor suppressor gene; myelodysplastic syndrome; fluorescence in situ hybridization; proportional hazards model; cytopenia; myelodysplastic syndromes; genetic heterogeneity; platelet count; log rank test; tp53; acute myeloid leukemia; cancer prognosis; high throughput sequencing; very elderly; prognosis; human; male; female; article; phantm combined phenotype score |
| Journal Title: | Cancers |
| Volume: | 13 |
| Issue: | 21 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2021-11-01 |
| Start Page: | 5502 |
| Language: | English |
| DOI: | 10.3390/cancers13215502 |
| PROVIDER: | scopus |
| PMCID: | PMC8582962 |
| PUBMED: | 34771665 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2021 -- Source: Scopus |
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