From Guardian to Culprit: The Functional Dichotomy of p53 in Tumor Suppression and Oncogenesis

p53 (TP53), widely known as the “guardian of the genome,” is one of the most frequently altered genes in human cancer. While its canonical tumor-suppressive functions, ranging from DNA repair and cell cycle arrest to apoptosis, are well established, the diverse consequences of TP53 alterations across cancer types remain incompletely understood. Importantly, distinct classes of TP53 mutations exhibit markedly different biological behaviors, including dominant-negative effects, gain-of-function activities, and loss through deletions or multi-hit events. These differences underscore the need for a systematic and context-aware understanding of TP53 alterations at the genomic level.Recent advances in cancer genomics have enabled large-scale characterization of TP53 mutation landscapes, revealing substantial heterogeneity in mutation type, allelic status, and co-occurring genomic events. Integrating these data with functional and clinical outcomes offers an opportunity to move beyond a generalized view of mutant p53 toward a more precise stratification of its oncogenic roles.This Research Topic aims to provide a comprehensive, genomics-driven perspective on TP53 alterations in cancer. We seek to highlight how different mutation classes and genomic contexts shape tumor behavior, influence oncogenicity, and impact therapeutic response. By combining computational modeling, large-scale genomic analyses, and experimental validation, this issue will bridge molecular mechanisms with systems-level insights.We invite submissions addressing, but not limited to, the following themes:• Systematic classification and functional annotation of TP53 mutations (e.g., dominant-negative, gain-of-function, loss-of-function).• Genomic contexts of TP53 alterations, including deletions, copy number changes, and co-mutation patterns.• Integrative and computational approaches linking TP53 mutation types to clinical outcomes and tumor evolution.• Multi-omics and single-cell approaches to resolve TP53-driven heterogeneity in cancer.• Therapeutic implications of TP53 mutation stratification, including precision oncology approaches targeting specific mutation classes.By emphasizing mutation-level resolution and genomic context, this Research Topic aims to advance a more nuanced and clinically relevant understanding of TP53 in cancer. Topic editors: Sharma Pratibha, Sunil Singh, Lakshay Malhotra, DR. SANKAT MOCHAN Source: https://www.frontiersin.org/research-topics/78915/from-guardian-to-culprit-the-functional-dichotomy-of-p53-in-tumor-suppression-and-oncogenesis