ReviewCell death and differentiation2018
Why are there hotspot mutations in the TP53 gene in human cancers?
Review in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04872036 (Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens), which is not on this map. Cited by 374 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens
Who cites it
374 citing papers in PubMed, 1 synthesis or guideline pooled it, 604 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Osimertinib plus chemotherapy versus osimertinib for patients with advanced NSCLC with concomitant EGFR and TP53 mutations: a prospective cohort study.Scientific reports · 2025Trial
- Article
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Impact of differentTranslational lung cancer research · 2026Article
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Mutant p53 gains RNA-binding activity to reprogram translation and mitochondrial function.Cell reports · 2026Article
- Review
- A human ex vivo model of radiation-induced skin injury recapitulates p53-driven profibrotic response to radiotherapy.JCI insight · 2026Article
- Nuclear adenosine metabolism defines a metabolic vulnerability unmasked by TP53 loss.bioRxiv : the preprint server for biology · 2026Article
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Article
- Decoding protein-phospholipid interaction networks in cancer: the role of acyl-chain remodeling.RSC chemical biology · 2026Review
- The p53 Isoforms as Potential Biomarkers in Different Cancer Entities.International journal of molecular sciences · 2026Review
- Targeting p53 in Cancer: Functional States, Therapeutic Strategies, and Clinical Progress.Cancers · 2026Review
- Lipid transfer proteins and PI4KIIα initiate nuclear p53-phosphoinositide signaling.The Journal of biological chemistry · 2026Article
- ROWVA: A Structure-Based Metric for Predicting the Pathogenicity of Protein Variants Using Alphafold2.Cancer science · 2026Article
- Advances in Brain Tumor Biomarkers: From Molecular Profiling to Liquid Biopsy and AI-Driven Detection.Cancers · 2026Review
- Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer.Journal of gastroenterology · 2026Article
- From mechanism to medicine: CRISPR‒Cas9 delivery strategies, therapeutic applications and translation challenges.Discover nano · 2026Review
314 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The p53 gene contains homozygous mutations in ~50-60% of human cancers. About 90% of these mutations encode missense mutant proteins that span ~190 different codons localized in the DNA-binding domain of the gene and protein. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates the p53 transcriptional pathway. Eight of these mutations are localized in codons that account for ~28% of the total p53 mutations and these alleles appear to be selected for preferentially in human cancers of many tissue types. This article explores the question 'Why are there hotspot mutations in the p53 gene in human cancers?' Four possible reasons for this are considered; (1) the hotspot mutant alleles produce a protein that has a highly altered structure, (2) environmental mutagens produce allele-specific changes in the p53 gene, (3) these mutations arise at selected sites in the gene due to a specific DNA sequence, such as a methylated cytosine residue in a CpG dinucleotide, which has a higher mutation rate changing C to T nucleotides, (4) along with the observed change in mutant p53 proteins, which produce a loss of function (DNA binding and transcription), some mutant proteins have an allele-specific gain of function that promotes cancer. Evidence is presented that demonstrates the first three possibilities all contribute some property to this list of hotspot mutations. The fourth possibility remains to be tested.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.