TP53 R273H

In conclusion, our research suggests that R273H and R273C each have unique stability and self-assembly properties. This understanding might assist researchers in better comprehending the function of the p53 protein and its importance in cancer.Communicated by Ramaswamy H. Sarma.

The fragments occupy the central cavity and mimic the ring system of the WT tyrosine lost by the mutation. Surpassing previously reported noncovalent ligands, SN001 stabilized T-p53C-Y220C concentration-dependently up to 4.45 °C and, due to its small size, represents a promising starting point for optimization.

We observed mutation-specific tumor phenotypes across tp53 mutants with associated diverse transcriptomic and DNA methylome profiles in tp53 mutant larvae, impacting metabolism, cell signalling, and biomacromolecule synthesis and degradation. These tp53 zebrafish mutants demonstrate fidelity to their human counterparts and provide new insights into underlying tumorigenesis mechanisms and kinetics that suggest metabolic rewiring and cellular signalling changes occur prior to tumor initiation, which will guide targeted therapeutics for LFS.

We correlated the potential impact of mutation in target gene transcription and regulation with nucleosomal DNA and RNA-Pol II complexes. We have discussed the impact of mutation at post-translational modification sites in the structure and function of p53 highlighting the potential therapeutic drug targets with tremendous clinical applications.

Our study elucidates the mutant-specific impact of p53R270H and p53R172H on metabolism of PDAC cancer cells, highlighting the need to shift from viewing p53 mutant variants as a homogeneous group of entities to a systematic assessment of each specific p53 mutant protein. Moreover, our finding underscores the importance of further exploring the significance of p53 mutant proteins using models that more accurately reflect tumor ecology.

This report emphasizes the crucial role of meticulous sampling and histopathologic examination of the fallopian tube, including the fimbriae, in all salpingectomy specimens. Furthermore, the case highlights the broad spectrum of morphologies encountered in HGSC, including mucinous differentiation. HGSC should be in the differential diagnosis when encountering mucin-producing high-grade carcinoma.

Mutational hotspots are a recurrent feature in both genes which, due to positive selection during tumorigenesis, can be potentially exploited by targeted treatments, as has been demonstrated by the US Food and Drug Administration (FDA)-approved PI3K inhibitor alpelisib in advanced hormone-receptor positive (HR+) breast cancer... The AGENA ClearSEEK PIK3CA and TP53 Panels combine low hands-on time requirements with accurate data assessment, and provide a reliable tool for clinical trial evaluation of known actionable PIK3CA mutations and response to PI3K inhibitors in breast cancer, as well as for investigating the oncogenic activities of TP53 hotspot mutations and patient selection e.g., for cell cycle targeting therapies.

The lesion was diagnosed as persistent THOA. This case report discusses the salient features, genetic profile, and prognosis of this uncommon lesion.

Here, we introduced a peptide that disrupts the PC4-R273Hp53 interaction to tumor cells bearing the R273HTP53 gene, which led to a lowering of MDR1 expression and abrogation of drug resistance in a mutant-specific manner. The results suggest that the PC4-R273Hp53 interaction may be a promising target for reducing proliferation and drug resistance in tumors.

NSCLC cell lines with the mutant R273H allele demonstrated increased susceptibility and apoptosis to proteasome inhibitors. These data suggest that proteasome inhibitors could have therapeutic implications in some subsets of TP53 mutated NSCLC.

These alterations in cell motility were closely associated with actin cytoskeleton restructuring, favoring γ-actin, and coincided with ERK1/2-mediated signaling activation, unveiling an innovative regulatory mechanism in malignancy progression. Cancer cell aggressiveness, driven by actin cytoskeleton reorganization and a shift towards γ-actin predominance, may be regulated by p53 dysfunction, thereby providing novel insight into tumor progression mechanisms.

In this cohort, most AA-NMTC patients exhibit favorable outcomes after therapeutic intervention given at cancer centers, suggesting that healthcare disparity is the major contributor for worse prognoses among AA-NMTC patients. Nevertheless, the clinical impact of PPGVs that might facilitate acquisition of TP53 tumor mutations, and/or PPGVs that predispose individuals to adverse cardiovascular events which could be exacerbated by therapy-induced cardiotoxicity, need to be further explored. Integrated analysis of PPGV/PPSV profiles among NMTC patients with different stages of disease may help to identify NMTC patients who require close monitoring or proactive intervention.