Next-Generation Sequencing Reveals a Diagnostic and Prognostic Role of the TP53 R273C Mutation in Lower-Grade, IDH-Mutant Astrocytomas
The current WHO grading of central nervous system tumors relies exclusively on histopathological criteria for diagnosing lower-grade, IDH-mutant astrocytomas (LGIMAs), overlooking genetic features. The TP53 R273C mutation, frequently observed in brain tumors, may influence LGIMA biology and aggressi...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:dnet:r-fisabio___::aa1884ebdc1bde520180810990df7dfe |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/20795 https://www.scopus.com/inward/record.uri?eid=2-s2.0-105024630073&doi=10.3390%2fijms262311483&partnerID=40&md5=81ddb7b7b465c7addbd6f0b6861582fe |
| Access Level: | acceso abierto |
| Palabra clave: | IDH-mutant astrocytomas Ki-67 lower-grade next-generation sequencing TCGA TP53 R273C mutation Adult Aged Astrocytoma Brain Neoplasms Female High-Throughput Nucleotide Sequencing Humans Isocitrate Dehydrogenase Ki-67 Antigen Male Middle Aged Mutation Neoplasm Grading Prognosis Tumor Suppressor Protein p53 isocitrate dehydrogenase 1 isocitrate dehydrogenase 2 Ki 67 antigen protein p53 isocitrate dehydrogenase TP53 protein, human adult aged allele Article astrocytoma cancer classification cancer diagnosis cancer grading cancer prognosis cancer survival cell proliferation clinical article cohort analysis comorbidity female follow up gene frequency gene mutation high throughput sequencing histopathology human human tissue immunohistochemistry male middle aged mitosis molecular diagnosis neuropathology phenotype prediction prevalence sex difference tumor volume brain tumor diagnosis genetic |
| Sumario: | The current WHO grading of central nervous system tumors relies exclusively on histopathological criteria for diagnosing lower-grade, IDH-mutant astrocytomas (LGIMAs), overlooking genetic features. The TP53 R273C mutation, frequently observed in brain tumors, may influence LGIMA biology and aggressiveness. We analyzed 14 TP53-mutant LGIMAs using NGS. Five tumors (33.3%) carried the R273C mutation; these were mostly of grade 2 and all from female patients. Ki-67 levels in R273C-mutant tumors were higher compared with those in other TP53-mutant grade 2 tumors but lower than those in grade 3 tumors, which may suggest that R273C defines a more aggressive grade 2 profile. This mutation was linked to loss of the wild-type allele, supporting a loss-of-function mechanism. Its frequency was found to be potentially higher in women, and this sex-based difference reached statistical significance when incorporating TCGA LGIMA data. Overall, the R273C mutation, although mechanistically unclear, is more prevalent than other TP53 variants and defines a distinct biological subset of LGIMAs, marked by increased Ki-67 and female predominance. Incorporating TP53 and broader genetic profiling via NGS could improve our understanding of LGIMAs and support a refined classification system, enhancing diagnostic and prognostic accuracy. © 2025 by the authors. |
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