TP53 mutation

Our findings establish MAP3K1 and MAP2K4 as key tumor suppressors in BRCA that operate via the JNK2-p53-FOSL1 axis. Their inactivation provides an alternative mechanism for p53 pathway disruption, adhering to the "minimal necessary alteration" principle in cancer signaling. This study highlights the dual regulatory mechanisms controlling FRA1 expression and offers insights into breast cancer heterogeneity, with potential implications for targeted therapy and patient stratification.

EBV-GC is characterized by distinct clinicopathological and molecular features. Pathological examination, immunophenotyping, and NGS provide significant value for diagnosis and therapeutic direction.

Clinical proteomic analysis of platinum-resistant ovarian cancer tissues reveals tumor-specific factors and acquired resistance pathways linked to p53 mutations. Our findings elucidate the multilayered regulatory landscape of p53 mutations and identify potential risk factors for platinum resistance associated with these mutations.

These findings highlight the need to molecularly characterize these lesions as there is no specific histologic finding to identify cases that harbour different pathogenic alterations in specific genes.

In this Middle Eastern cohort, no consistent molecular or clinical disparities across most parameters. These findings suggest the timing of metastasis may not independently influence prognosis and highlight the relevance of individualized, biology-driven management strategies.

Gastric tumors can bypass niche dependence by acquiring KRAS-MAPK-SMAD2/3-driven epithelial WNT secretion. Targeting this axis-through MAPK inhibition, SMAD2/3 blockade, or suppression of WNT secretion-may represent a therapeutic vulnerability in gastric cancer and other KRAS-high malignancies.

P3, N=255, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Dec 2025 --> Mar 2026

New technologies and improved fidelity of model systems are uncovering the functional consequences caused by p53 mutations at the molecular, cellular, and tissue levels. In a new era of precision medicine, with the context of recent success in targeting genetic mutations, ongoing and future understanding of fundamental mutant p53 biology is of paramount importance.

Foamy cell change is a distinctive cytoplasmic alteration in STIC and HGSC. The presence of this histologic feature should prompt immunohistochemical studies to confirm serous differentiation.

Adjuvant drugs can reduce inflammation and neuropathic pain, including corticosteroids, gabapentinoid agents such as gabapentin or pregabalin, lidocaine patches, tricyclic antidepressants such as amitriptyline, nortriptyline, and desipramine, or selective serotonin-norepinephrine reuptake inhibitors such as duloxetine and venlafaxine. The present investigation aims to synthesize currently available data on periosteal osteosarcomas, including common clinical, histologic, and radiographic presentations. In addition, this review aims to further examine the potential for biomarkers and provide recommendations for treatment and future research direction.

Our study demonstrates that the majority (86%) of SLCTs with heterologous RMS harbor double DICER1 mutations (a hotspot mutation and a nonsense or frameshift loss-of-function mutation), supporting the existing knowledge on DICER1 mutations associated with RMS heterologous elements, the presence of which should trigger genetic counselling. Our findings also suggest that molecular alterations other than DICER1, namely, TERT promoter and TP53 mutations, may contribute to component-specific oncogenic transformation.

This molecular signature implies potential synergistic effects between chromatin instability, compromised DNA damage repair mechanisms, and augmented immunogenicity. Through comprehensive genomic analysis, we elucidate the biological significance of this mutational landscape and discuss its therapeutic implications, aiming to advance precision diagnosis and guide innovative treatment strategies for SMARCA4-DNSCLC.