Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Squamous cell lung cancer is a major histotype of non-small cell lung cancer (NSCLC) that is distinct from lung adenocarcinoma. We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer. We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts. We also found four SNVs located within splicing sites. We verified 62 of the SNVs (51 missense, 10 nonsense and 1 splicing-site mutation) and 10 of the INDELs as somatic mutations in lung cancer tissue. Sixteen of the mutated genes were also mutated in at least one patient with a different type of lung cancer in the Catalogue of Somatic Mutation in Cancer (COSMIC) database. Four genes (LPHN2, TP53, MYH2 and TGM2) were mutated in approximately 10% of the samples in the COSMIC database. We identified two missense mutations in C10orf137 and MS4A3 that also occurred in other solid-tumor tissues in the COSMIC database. We found another somatic mutation in EP300 that was mutated in 4.2% of the 2,020 solid-tumor samples in the COSMIC database. Taken together, our results implicate TP53, EP300, LPHN2, C10orf137, MYH2, TGM2 and MS4A3 as potential driver genes of squamous cell lung cancer.
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PMID:Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers. 2379 14

Mutations in the transcription factor p53 are among the most common genetic alterations in human cancer, and missense p53 mutations in cancer cells can lead to aggressive phenotypes. So far, only few studies investigated transcriptional reprogramming under mutant p53 expression as a means to identify deregulated targets and pathways. A review of the literature was carried out focusing on mutant p53-dependent transcriptome changes with the aims of (i) verifying whether different p53 mutations can be equivalent for their effects, or whether there is a mutation-specific transcriptional reprogramming of target genes, (ii) understanding what is the main mechanism at the basis of upregulation or downregulation of gene expression under the p53 mutant background, (iii) identifying novel candidate target genes of WT and/or mutant p53 and (iv) defining cellular pathways affected by the mutant p53-dependent gene expression reprogramming. Nearly 600 genes were consistently found upregulated or downregulated upon ectopic expression of mutant p53, regardless of the specific p53 mutation studied. Promoter analysis and the use of ChIP-seq data indicate that, for most genes, the expression changes could be ascribed to a loss both of WT p53 transcriptional activation and repressor functions. Pathway analysis indicated changes in the metabolism/catabolism of amino acids such as aspartate, glutamate, arginine and proline. Novel p53 candidate target genes were also identified, including ARID3B, ARNT2, CLMN, FADS1, FTH1, KPNA2, LPHN2, PARD6B, PDE4C, PIAS2, PRPF40A, PYGL and RHOBTB2, involved in the metabolism, xenobiotic responses and cell differentiation.
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PMID:More targets, more pathways and more clues for mutant p53. 2381 66