TP53 R273C

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.

This is the largest study to investigate the landscape of immunogenic neoantigens in BC and PC. The frequency of high-level binding affinity neoantigens was relatively low and associated with relatively lower TIS scores in MSS tumors, which may contribute to the immunogenic cold TME characterizing these tumor types.

Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model.

Further, comparative analyses of large transcriptomics datasets on breast cancer cell lines and tumors suggest that dysregulation of the Hippo/YAP/TAZ pathway plays a key role in driving the cellular phenotypes towards basal-like in the presence of more aggressive p53 mutants. Overall, our study describes distinct gain-of-function impacts on protein functions, transcriptional profiles, and cellular behaviors of different p53 missense mutants, which contribute to clinical phenotypic heterogeneity of triple-negative breast tumors.

P2, N=60, Not yet recruiting, Sun Yat-sen University

NGS analysis of TETs revealed several somatic variants in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. TCs showed greater genetic dysregulation than TMs. KIT alterations in TCs have potential as therapeutic targets.

Material and Methods We analysed preoperative core biopsy samples of 20 patients with MRSTS who received 5×5 Gy radiotherapy combined with three cycles of doxorubicin-ifosfamide chemotherapy in a phase II clinical trial (NCTXXXXXXXX). D Undifferentiated pleomorphic sarcoma CDK4 Amplification - - D Dedifferentiated liposarcoma CDK4 Amplification - - E Undifferentiated pleomorphic sarcoma RB1 Nonsense mutation c.958C>T p.R320* D Myxofibrosarcoma AKT2 Amplification - - D Undifferentiated pleomorphic sarcoma PTEN Gene deletion - - D Undifferentiated pleomorphic sarcoma PTEN Gene deletion - - E Pleomorphic liposarcoma PTEN Gene deletion - - D Myxofibrosarcoma NF1 Nonsense mutation c.3520C>T p.Q1174* D Malignant peripheral nerve sheath tumor NF1 Nonsense mutation c.1278G>A p.W426* D Malignant peripheral nerve sheath tumor Conclusion The detection of known mutations in MRSTS suggests poor pathological response to neoadjuvant radiochemotherapy. Identified mutations may indicate new therapeutic targets in the treatment of MRSTS.

In CRC, non-GOF mTP53 was prevalent in more than half of all cases. Compared to GOF mTP53, predictive biomarkers of response to immune checkpoint inhibitors (TMB and MSI-H/dMMR) were higher in this cohort albeit still relatively rare. Otherwise, differences in molecular signatures between GOF and non-GOF mTP53 did not contain clinically meaningful differences.

These results confirm the non-equivalence of p53 mutations in the context of hepatocellular carcinoma and suggest the acquisition of a gain-of-function phenotype for certain mutants. Experiments are ongoing to validate this observation and identify the molecular mechanisms involved in this process.