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Role of TP53 Mutation in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 749

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Department of Obstetrics and Gynecology, Wakayama Medical University, School of Medicine, Wakayama, Japan
Interests: ovarian cancer; gene therapy; genome editing; adeno-associated virus; immune checkpoint
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Special Issue Information

Dear Colleagues,

The tumor suppressor p53 is one of the most extensively studied proteins in cancer biology. Unlike many tumor suppressors that are inactivated by deletion or truncation, TP53 is most frequently altered by missense mutations, resulting in the expression of mutant p53 proteins with distinct biological properties. Accumulating evidence indicates that mutant p53 not only loses its canonical tumor-suppressive functions but also acquires oncogenic gain-of-function activities that actively drive cancer initiation, progression, metastasis, and therapeutic resistance.

Recent advances have revealed that mutant p53 influences multiple cancer-related processes, including transcriptional reprogramming, chromatin remodeling, metabolic adaptation, genomic instability, and interactions with signaling pathways and the tumor microenvironment. Moreover, mutant p53 has emerged as a promising therapeutic target, with growing interest in strategies aimed at mutant p53 reactivation, degradation, synthetic lethality, and immunological targeting.

This Special Issue, “Role of TP53 Mutation in Cancer,” aims to provide a comprehensive platform for basic, translational, and clinical studies that deepen our understanding of mutant p53 biology and its implications across diverse cancer types. We welcome original research articles and high-quality reviews addressing molecular mechanisms, novel model systems, biomarker development, therapeutic vulnerabilities, and emerging clinical strategies targeting mutant p53. By integrating mechanistic insights with translational relevance, this Special Issue seeks to highlight how mutant p53 research can inform innovative approaches to cancer diagnosis and treatment.

Dr. Naoyuki Iwahashi
Guest Editor

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Keywords

  • TP53 mutation
  • p53 aggregate
  • gain-of-function
  • cancer progression
  • transcriptional reprogramming
  • therapeutic targeting
  • biomarker
  • translational research
  • precision oncology

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Published Papers (1 paper)

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Research

13 pages, 11799 KB  
Article
Molecular Characterization of TP53 Variants in Exons 4-8 and p53 Immunoexpression in a Mexican Colorectal Cancer Cohort
by Fernando Daniel García-Ayala, María de la Luz Ayala-Madrigal, Jorge Peregrina-Sandoval, José Miguel Moreno-Ortiz, Anahí González-Mercado, Ramón Antonio Franco-Topete, Jesús Alonso Valenzuela-Pérez, Nelly Margarita Macías-Gómez, Beatriz Armida Flores-López and Melva Gutiérrez-Angulo
Cancers 2026, 18(11), 1678; https://doi.org/10.3390/cancers18111678 - 22 May 2026
Viewed by 421
Abstract
Background/Objectives: Colorectal cancer (CRC) represents a major public health problem in Mexico and is among the malignancies with the highest morbidity and mortality. Alterations in TP53 are frequent molecular events in tumors with chromosomal instability; however, information on TP53 variants in the Mexican [...] Read more.
Background/Objectives: Colorectal cancer (CRC) represents a major public health problem in Mexico and is among the malignancies with the highest morbidity and mortality. Alterations in TP53 are frequent molecular events in tumors with chromosomal instability; however, information on TP53 variants in the Mexican population, particularly in exons 4-8, remains limited. Exons 4-8 comprise the main coding region of the p53 DNA-binding domain; therefore, this study aimed to identify TP53 variants in these regions and evaluate p53 protein expression by immunohistochemistry in sporadic CRC. Methods: Tumor samples from 142 patients who underwent surgical resection without neoadjuvant treatment were analyzed. DNA was extracted from tumor tissue. TP53 exons 4-8 were amplified by polymerase chain reaction (PCR), and variants were identified by Sanger sequencing. p53 immunohistochemistry was performed in 40 tumors and 36 adjacent tissues, and nuclear expression was assessed using the Immunoreactivity Score. Results: Forty-three heterozygous variants were identified in 106/142 patients, representing 75% of the cohort. Thirty-one patients carried oncogenic variants, mainly clustered within the DNA-binding domain and involving hotspot residues such as Arg175, Tyr220, Gly245, Arg248, Arg273, and Arg282. Nuclear p53 expression was observed in 9/40 tumors, whereas all adjacent tissues were negative. Conclusions: TP53 alterations in exons 4-8 are frequent and heterogeneous in this Mexican cohort. Integrating mutational profiling with p53 immunohistochemistry provides complementary information for the biological interpretation of these tumors, including variants of translational interest. Full article
(This article belongs to the Special Issue Role of TP53 Mutation in Cancer)
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