ArticleJournal of the National Cancer Institute2021
Effect of the p53 P72R Polymorphism on Mutant TP53 Allele Selection in Human Cancer.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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23 citing papers in PubMed, 30 citations in OpenAlex.
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- New cell lines expanding the diversity of Ewing sarcoma models.International journal of cancer · 2026Article
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- Comparative outcome and prognostic factor analysis among MDS/AML patients with TP53 mutations, snps, and wild type.Human genomics · 2025Article
- The therapeutic potential of pegylated arginase I treatment in glioblastoma.Scientific reports · 2025Article
- Evaluating Liquid Biopsy for Circulating Tumor DNA (ctDNA) Detection as a Complementary Diagnostic Tool in Thyroid Cancer Among Ecuadorian Women.International journal of molecular sciences · 2025Article
- Association of P53 Codon 72 Polymorphism with Ovarian Cancer: An Institutional Study.Asian Pacific journal of cancer prevention : APJCP · 2025Article
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- Scalable co-sequencing of RNA and DNA from individual nuclei.Nature methods · 2025Article
- Identification of novel germline and somatic mutations associated with hepatocellular carcinoma by next-generation sequencing.Frontiers in pharmacology · 2025Article
- Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals.Chemical reviews · 2024Review
- Efficacy of novel agents against cellular models of familial platelet disorder with myeloid malignancy (FPD-MM).Blood cancer journal · 2024Article
- DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis.Cancers · 2024Article
- Association of the rs1042522 SNP with prostate cancer risk: a study of cancer tissues, primary tumor cultures, and serum samples from a Spanish Caucasian population.Frontiers in oncology · 2024Article
- Establishment and Characterization of a TP53-Mutated Eyelid Sebaceous Carcinoma Cell Line.Investigative ophthalmology & visual science · 2023Article
- Relationship Between Genetic Polymorphisms in Cell Cycle Regulatory Gene TP53 and Polycystic Ovarian Syndrome: A Case-Control Study and In Silico Analyses.Biochemical genetics · 2023Article
- Association of Chromosome 17 Aneuploidy,Cancers · 2023Article
- Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer.International journal of molecular sciences · 2023Article
- TheBiomedicines · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundTP53 mutations occur in more than 50% of cancers. We sought to determine the effect of the intragenic P72R single nucleotide polymorphism (SNP; rs1042522) on the oncogenic properties of mutant p53.
methodsP72R allelic selection in tumors was determined from genotype calls and a Gaussian distributed mixture model. The SNP effect on mutant p53 was determined in p53-negative cancer cell lines. RNA-sequencing, chromatin immunoprecipitation, and survival analysis were performed to describe the SNP effect. All statistical tests were 2-sided.
resultsAmong 409 patients with germline heterozygous P72R SNP who harbored somatic mutations in TP53, we observed a selection bias against missense TP53 mutants encoding the P72 SNP (P = 1.64 x 10-13). Exogenously expressed hotspot p53 mutants with the P72 SNP were negatively selected in cancer cells. Gene expression analyses showed the enrichment of p53 pathway genes and inflammatory genes in cancer cells transduced with mutants encoding P72 SNP. Immune gene signature is enriched in patients harboring missense TP53 mutations with homozygous P72 SNP. These patients have improved overall survival as compared with those with the R72 SNP (P = .04).
conclusionThis is the largest study demonstrating a selection against the P72 SNP. Missense p53 mutants with the P72 SNP retain partial wild-type tumor-suppressive functions, which may explain the selection bias against P72 SNP across cancer types. Ovarian cancer patients with the P72 SNP have a better prognosis than with the R72 SNP. Our study describes a previously unknown role through which the rs1042522 SNP modifies tumor suppressor activities of mutant p53 in patients.
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