ArticleMolecular cancer research : MCR2014
Transcriptomes and shRNA suppressors in a TP53 allele-specific model of early-onset colon cancer in African Americans.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- PRDM Proteins Orchestrate Colorectal Cancer Tumorigenesis.International journal of molecular sciences · 2026Review
- PRDM1-mediated epigenetic and transcriptional repression mechanisms: a key hub in immune differentiation, tumor progression, and inflammatory responses.Frontiers in immunology · 2026Review
- The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-SidedGastrointestinal disorders (Basel, Switzerland) · 2024Article
- Article
- PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Lung cancer health disparities.Carcinogenesis · 2018Review
- Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Article
- Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin?Trends in cancer · 2017Review
- The genetics and molecular biology of colonic neoplasia: practical implications for the clinician.Current opinion in gastroenterology · 2017Review
- Genomic comparison of early-passage conditionally reprogrammed breast cancer cells to their corresponding primary tumors.PloS one · 2017Article
- Genetic Modifiers of the p53 Pathway.Cold Spring Harbor perspectives in medicine · 2016Review
- Association of p53 rs1042522, MDM2 rs2279744, and p21 rs1801270 polymorphisms with retinoblastoma risk and invasion in a Chinese population.Scientific reports · 2015Article
- Identification of TRIML2, a novel p53 target, that enhances p53 SUMOylation and regulates the transactivation of proapoptotic genes.Molecular cancer research : MCR · 2015Article
- Advanced Invasive Extramammary Paget's Disease Concomitant with Cecal Cancer Possessing Rare Variant of TP53 Single Nucleotide Polymorphism.Case reports in oncologyArticle
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Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
unlabelledAfrican Americans are disproportionately affected by early-onset, high-grade malignancies. A fraction of this cancer health disparity can be explained by genetic differences between individuals of African or European descent. Here the wild-type Pro/Pro genotype at the TP53Pro72Arg (P72R) polymorphism (SNP: rs1042522) is more frequent in African Americans with cancer than in African Americans without cancer (51% vs. 37%), and is associated with a significant increase in the rates of cancer diagnosis in African Americans. To test the hypothesis that Tp53 allele-specific gene expression may contribute to African American cancer disparities, TP53 hemizygous knockout variants were generated and characterized in the RKO colon carcinoma cell line, which is wild type for TP53 and heterozygous at the TP53Pro72Arg locus. Transcriptome profiling, using RNAseq, in response to the DNA-damaging agent etoposide revealed a large number of Tp53-regulated transcripts, but also a subset of transcripts that were TP53Pro72Arg allele specific. In addition, a shRNA-library suppressor screen for Tp53 allele-specific escape from Tp53-induced arrest was performed. Several novel RNAi suppressors of Tp53 were identified, one of which, PRDM1β (BLIMP-1), was confirmed to be an Arg-specific transcript. Prdm1β silences target genes by recruiting H3K9 trimethyl (H3K9me3) repressive chromatin marks, and is necessary for stem cell differentiation. These results reveal a novel model for African American cancer disparity, in which the TP53 codon 72 allele influences lifetime cancer risk by driving damaged cells to differentiation through an epigenetic mechanism involving gene silencing. IMPLICATIONS: TP53 P72R polymorphism significantly contributes to increased African American cancer disparity.
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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.