RB1 mutation

It was more extensive in poorly differentiated areas and showed an inverse correlation with the proliferation rate. Our histopathologic, immunohistochemical and genetic findings provide further evidence that Bowen disease may act as a precursor for the rosette-forming component of the Wnt/β-catenin-activated carcinoma and that there is an inverse correlation between CDX2 expression and the proliferation rate.

Germline changes associated with malignancies were examined using next-generation sequencing (NGS). There were no germline alterations discovered, suggesting no predisposition to develop cancer. Three pathogenic/likely pathogenic heterozygous variants were found in the patient by carrier screening. Absence of germline RB1 mutations or other hereditary cancer syndromes implicates treatment-related factors (chemotherapy/radiotherapy) as the primary driver of sequential malignancies. Nonhereditary retinoblastoma (RB) survivors have a lower risk of secondary malignancies (SMNs) compared to their hereditary counterparts. Chemotherapy, especially alkylating agents, increases the risk of secondary acute myelogenous leukemia (AML) and other leukemias and lymphomas due to its mutagenic effects and genetic factors. Although RB survivors rarely develop secondary cancers, the limited patient numbers and short follow-up periods may influence SPC risk assessments. Continuous monitoring and personalized follow-up care are crucial for managing long-term risks in these survivors. This research emphasizes the essential importance of ongoing monitoring and follow-up for survivors of retinoblastoma (RB) to identify and address secondary malignancies (SMNs), improve the management of long-term complications, and enhance both life expectancy and quality of life.

Histopathological examination confirmed leiomyosarcoma, and the patient underwent four chemotherapy cycles with doxorubicin, followed by surgical resection...This case underscores the importance of personalized treatment strategies, including surgical decision-making, chemotherapy, and molecular characterization, in managing rare tumors like IVC leiomyosarcoma. Further research is needed to explore potential oncogenic targets and improve prognosis.

Tarlatamab appeared effective when added to osimertinib. Further analysis of the combination of bispecific DLL3 T-cell engager and EGFR tyrosine kinase inhibitor is warranted to confirm these findings.

MCC oncogenesis and treatment response transcend viral status. While mutational analysis confirms previous findings, assessment of the transcriptome and tumor microenvironment suggests alternate therapeutic targets.

These findings underscore the potential of multimodal artificial intelligence (AI) tools to advance precision oncology, particularly in resource-limited settings. Further validation in larger, diverse cohorts is warranted.

DIS accelerates the malignant progression of shRB1 CRPC, mediated by tumorigenic SASP, especially IL-20 enrichment. Notably, we identifies a novel FOXA1-IL-20-IL20Rβ axis that drives M2-like macrophage polarization and contributes to tumor aggressiveness and docetaxel resistance. Importantly, senolytic agent ABT-263 not only selectively eliminated shRB1-DIS cells but also restricted expression of tumorigenic SASPs, thereby restoring sensitivity to docetaxel. Wherein, IL-20 is inhibited through its interaction with ABT-263. These results provide a novel mechanistic rationale for using senolytic therapies to mitigate SASP-driven malignancy and improve treatment response in RB1-deficient CRPC.

(Conclusions) DNA methylation and histone acetylation play a crucial role in the epigenetic regulation of genes implicated in retinoblastoma. Their dysregulation promotes tumorigenesis, and targeting these mechanisms represents a promising avenue for novel diagnostic and therapeutic strategies in pediatric oncology.

Finally, we outline future research directions. Future studies should unravel transformation mechanisms, conduct rigorous randomized trials, and develop precision interventions, paving new avenues for improved patient outcomes.​.

Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies.

This study presents the first palmitoylation-related prognostic model for BLCA, highlighting GRK5 methylation as a potential biomarker for early detection and personalized treatment.

We discuss herein the novel approach of population screening, the rationale for newborn testing for RB1 mutations, the incidence of expected cases, the reliability of the test and its costs. The next step is to move to a nation-scale population; this initiative marks a landmark in retinoblastoma patients' care.