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• W2943911071 abstract "Abstract Lung cancer is the leading cause of cancer-related deaths in the USA, and alterations in the tumor suppressor gene TP53 are the most frequent somatic mutation among all histologic subtypes of lung cancer. Mutations in TP53 frequently result in a protein that exhibits not only loss of tumor suppressor capability but also oncogenic gain-of-function (GOF). The canonical p53 hotspot mutants R175H and R273H, for example, confer upon tumors a metastatic phenotype in murine models of mutant p53. To the best of our knowledge, GOF phenotypes of the less often studied V157, R158 and A159 mutants—which occur with higher frequency in lung cancer compared with other solid tumors—have not been defined. In this study, we aimed to define whether the lung mutants are simply equivalent to full loss of the p53 locus, or whether they additionally acquire the ability to drive new downstream effector pathways. Using a publicly available human lung cancer dataset, we characterized patients with V157, R158 and A159 p53 mutations. In addition, we show here that cell lines with mutant p53-V157F, p53-R158L and p53-R158P exhibit a loss of expression of canonical wild-type p53 target genes. Furthermore, these lung-enriched p53 mutants regulate genes not previously linked to p53 function including PLAU. Paradoxically, mutant p53 represses genes associated with increased cell viability, migration and invasion. These findings collectively represent the first demonstration that lung-enriched p53 mutations at V157 and R158 regulate a novel transcriptome in human lung cancer cells and may confer de novo function." @default.
• W2943911071 created "2019-05-16" @default.
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• W2943911071 date "2019-05-08" @default.
• W2943911071 modified "2023-09-27" @default.
• W2943911071 title "The lung-enriched p53 mutants V157F and R158L/P regulate a gain of function transcriptome in lung cancer" @default.
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• W2943911071 doi "https://doi.org/10.1093/carcin/bgz087" @default.
• W2943911071 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7316406" @default.
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