Data from Unique transcriptional profiles underlie osteosarcomagenesis driven by different p53 mutants

• DOI: 10.1158/0008-5472.c.6742372.v2
• Publication Date: 2024-09-16T10:27:04Z
• Authors: Dhruv Chachad; Lalit R. Patel; Carlos Vera. Recio; Rasoul Pourebrahim; Elizabeth M. Whitley; Wenyi Wang; Xiaoping Su; An Xu; Dung-Fang Lee; Guillermina Lozano

<div>Abstract<p>Missense mutations in the DNA binding domain of p53 are characterized as structural or contact based on their effect conformation protein. These show gain-of-function activities, such promoting increased metastatic incidence compared to loss, often mediated by interaction mutant with a set transcription factors. interactions largely context specific. In order understand mechanisms which drive osteosarcoma progression, we created mouse models, either p53R172H p53R245W expressed specifically osteoblasts, yielding tumor development. Survival significantly decreased and mice expressing mutants p53-null mice, suggesting gain function. RNA-sequencing primary osteosarcomas revealed vastly different gene expression profiles between tumors missense tumors. Further, each regulated unique transcriptomes pathways through distinct repertoire Validation assays showed that p53R245W, but not p53R172H, interacts KLF15 migration invasion cell lines promotes metastasis allogeneic transplantation models. Additionally, analyses p53R248W ChIP peaks enrichment motifs human osteoblasts. Taken together, these data identify action p53.</p></div>