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Frequent DPH3 promo...
Frequent DPH3 promoter mutations in skin cancers.
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Denisova, Evgeniya (author)
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Heidenreich, Barbara (author)
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Nagore, Eduardo (author)
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Rachakonda, P Sivaramakrishna (author)
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Hosen, Ismail (author)
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Akrap, Ivana (author)
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Traves, Víctor (author)
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García-Casado, Zaida (author)
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López-Guerrero, José Antonio (author)
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Requena, Celia (author)
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Sanmartin, Onofre (author)
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Serra-Guillén, Carlos (author)
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Llombart, Beatriz (author)
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Guillén, Carlos (author)
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Ferrando, Jose (author)
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Gimeno, Enrique (author)
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Nordheim, Alfred (author)
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Kumar, Rajiv (author)
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(creator_code:org_t)
- 2015-09-21
- 2015
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:34, s. 35922-35930
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http://www.ncbi.nlm....
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
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- Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Denisova, Evgeni ...
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Heidenreich, Bar ...
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Nagore, Eduardo
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Rachakonda, P Si ...
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Hosen, Ismail
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Akrap, Ivana
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show more...
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Traves, Víctor
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García-Casado, Z ...
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López-Guerrero, ...
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Requena, Celia
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Sanmartin, Onofr ...
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Serra-Guillén, C ...
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Llombart, Beatri ...
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Guillén, Carlos
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Ferrando, Jose
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Gimeno, Enrique
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Nordheim, Alfred
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Hemminki, Kari
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Kumar, Rajiv
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Oncotarget
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Lund University