TP53 mutation

Identifying patients with high Ki67 and mutational p53 together with TERT mutations may help predict potential recurrence in aGCT cases.

At the same time POLE-mutated endometrial carcinomas recur rarely and exhibit the excellent prognosis. Here we report the rare case of 65 y.o. female patient with endometrioid carcinoma sharing immunohistochemical and molecular features of TP53-aberrant, MMR deficient and POLE-mutated subtypes.

The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

This study provides new insights into overcoming resistance to BRAF and MAPK inhibitors, with implications for treating thyroid cancer and potentially other BRAF-mutant tumors. Future efforts will focus on high-throughput screening approaches to explore ANXA7-targeted therapeutic strategies for thyroid cancer.

Additionally, ATRX mutations were frequently associated with a more pronounced deviation of the median structures. To statistically validate the associations between MRI and the histopathological features of glioblastomas, further studies with larger cohorts are required.

In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics.

Novel combination treatments are also discussed as strategies to improve outcomes and overcome resistance. Understanding these molecular mechanisms is critical to advancing personalized treatment approaches in CRC and improving patient prognosis.

Improved survival was observed with transplantation in groups DP2, DP7, and DP9. These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.

Furthermore, we present the following two signaling pathways that we have identified: one based on the small G-protein ARF6 driven by KRAS/TP53 mutations, and the other based on the RNA-binding protein Arid5a mediated by inflammatory cytokines, which promote both metabolic reprogramming and immune evasion in pancreatic cancer. Finally, the striking diversity among pancreatic cancers in the relative importance of mutational burden and the tumor microenvironment, their clinical relevance, and the potential for novel therapeutic strategies will be discussed.

Lymphovascular space invasion, histotype 2 and p53 mutation showed a slight, but not statistically significant, tendency to be risk factors for SLN positivity. A deeper analysis with univariate uninominal logistic regression showed that high-grade EC is related to a greater probability of MACs, as shown in other studies, and that low-grade EC (grades 1 and 2) had a strong relationship with low-volume metastasis (LVM); further studies are needed to confirm these results.

To conclude, aside from p53, both CK17 and SOX2 can be of value for reaching an accurate diagnosis of HPV-independent VIN.

By underlining the role of a functional p53 in safeguarding skin cells from UVR-induced damage, this work underscores the potential significance of targeting mutp53, aiming to restore its wild-type-like activity (reactivation), as a protective strategy against skin cancer (SC), particularly NMSC. Most importantly, an interesting crosstalk between p53 and its vitamin D receptor (VDR) transcriptional target is also highlighted in the suppression of skin carcinogenesis, which opens the way to promising chemopreventive strategies involving synergistic combinations between mutp53 reactivators and vitamin D. Collectively, this review not only opens new avenues for future research, but also offers promising prospects for the development of novel beneficial approaches in the field of SC.

Our findings establish that TP53 mutations are linked to poorer oncologic outcomes in breast cancer across all subtypes. Yet, within the TP53-mutated group, the specific characteristics of TP53 mutations do not influence oncologic outcomes.

Combining cases from our oncology center and previous literature, we found that NSCLC patients with coexisting ALK fusion mutations and other mutations have poorer response to targeted therapy and poorer prognosis, and we also compared the efficacy rates of various types of coexisting mutations for different treatment regimens. Therefore, this review can help to evaluate the prognosis of NSCLC patients with coexisting mutations and the efficacy of targeted therapies and to find more favorable treatment options for patients with this type of coexisting mutations.

TP53 and NRAS mutations were associated with increased risk of death (hazard ratio = 3.98 and 5.50, respectively). In a survey of physicians at the participating centers, 63% reported that the genomic panel was clinically useful, particularly for assessing clinical risk and evaluating indications for hematopoietic stem cell transplantation.

Although metastatic AA tumors are less likely to shed tumor DNA into the blood relative to CRC, ctDNA profiling in AA has clinical utility.

Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

This study underscores the potential of DL algorithms to predict key genetic alterations, such as TP53 mutations, in BC. DL-based histopathological analysis represents a valuable tool for improving patient management and tailoring treatment approaches based on molecular biomarker status.

We observed distinct mutation patterns and clinical factors between LUAD and LUSC, and noted that patients with TMB≥10 and PD-L1≥50% exhibited enhanced immunotherapy effects. Combining TMB≥10 and PD-L1≥50% proved to be a more effective predictor of immunotherapy efficacy.

The ICC diagnostic criteria are clinically significant for determining AML prognosis. In line with the changing treatment paradigm for AML, future research is needed to continuously validate diagnostic and risk stratification systems.

Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

It remains uncertain if nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.

Oncogene mutations such as KRAS G12V and EGFR may have implications for cancer surveillance strategies and inform future treatment trials of stage I NSCLC.

MRD-guided duration of treatment may improve further outcomes, but longer clinical follow-up is needed before this approach is incorporated in clinical guidelines. The review gives an update on the impact of biological markers on outcomes with novel agents.

The expansion of mutant p53 clones in premalignant skin lesions associates with β-HPV loss. Thus, immunity to commensal HPVs contributes to the homeostasis of mutated normal skin, highlighting the role of virome-immune system interactions in preserving aging human tissues.

Thus, NCRT does not seem to induce a relevant number of new driver mutations or mutational burden. Genetic profiling implies the potential to support tumor-informed approaches and outcome estimation in future.

Our results indicate that 14-gene RNA-level assay is correlated with specific genetic mutations, including TP53, KRAS, and LRP1B. These insights provide a stronger foundation for integrating molecular risk assessment with clinical and imaging data, offering more comprehensive information to guide more targeted and effective adjuvant therapy strategies in the future management of lung cancer.

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC). In three cases of EGFR-L858R+V834L, other co-mutations, including TP53, CTNNB1, and RB1, were detected either before or after afatinib resistance. These results suggested that V834L cooperates with other coexisting mutations to influence the therapeutic efficacy of EGFR-TKIs.

These findings hold significant potential to refine treatment strategies, and enhance survival outcomes for NSCLC patients. By enabling a personalized therapeutic approach tailored to individual risk scores, this model may facilitate more precise decisions concerning immunotherapy and chemotherapy, thereby optimizing patient management and treatment efficacy.

Therefore, p53 target genes-Fas, DR-5, Puma, and PIDD-were transcriptionally upregulated, leading to activation of the caspase-3-GSDME axis and promoting etoposide-induced pyroptosis in various tumor cells. This study demonstrates a previously uncharacterized association between O-GlcNAcylation and chemotherapy-induced pyroptosis, offering potential therapeutic interventions for pyroptosis-related diseases.

CD47 and CTLA-4 expressions can be considered possible diagnostic and prognostic markers in EC. They were good markers of P53 mutation, and higher tumor grades and stages.

Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.

We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation + allelic deletion or a single mutation with variant allele frequency (VAF) ≥40%; TP53 low risk (TP53LR) included a single TP53 mutation VAF.

These findings indicate that GFPT1 is a novel prognostic biomarker and a predictive indicator of chemotherapy response in invasive breast carcinoma. GFPT1 influences mRNA translation, cell cycle regulation, and M2 macrophage infiltration, thereby promoting cancer cell proliferation and metastasis.

In this respect, RB1 loss has been implicated in the progression of MM through its influence on interleukin-6 (IL-6) secretion and cell proliferation. This review comprehensively summarizes the role of RB1 in MM and expounds on the potential of targeting RB1 as a therapeutic strategy for this malignancy.

With its sped-up epigenetic aging, gcGB presented as the epigenetic oldest GB variant in our cohort. Whereas the correlation between accelerated tumor-intrinsic epigenetic aging and cellular senescence in gcGB stays elusive, fostering epigenetic aging programs in GB might be of interest for future exploration of alternative treatment options in GB patients.

Higher CD8+ T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (p<0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.

Notably, C1 is more sensitive to anti-PD1 therapies and FTCD is a promising therapeutic target, particularly for C1 and C4. These findings provide new insights into classification-guided precision medicine.

During melanoma development in cdkn2b-/-/tp53-/- frogs, the occurrences of epithelial-to-mesenchymal transition, the reactivation of pigment cell progenitor cell transcriptional states, and the activation in the MAPK, NF-kB, PI3K-Akt, and TGF-β signaling pathways were noted. Overall, cdkn2b-/-/tp53-/- Xenopus tropicalis provides a vertebrate model for investigating the development of CDKN2A germline mutation-induced hereditary melanoma, contributing to the exploration of the pathogenesis of hereditary melanoma in humans.

This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.

P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Dec 2025