Advanced

Frequent DPH3 promoter mutations in skin cancers.

Denisova, Evgeniya; Heidenreich, Barbara; Nagore, Eduardo; Rachakonda, P Sivaramakrishna; Hosen, Ismail; Akrap, Ivana; Traves, Víctor; García-Casado, Zaida; López-Guerrero, José Antonio and Requena, Celia, et al. (2015) In Oncotarget 6(34). p.35922-35930
Abstract
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;... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncotarget
volume
6
issue
34
pages
35922 - 35930
publisher
Impact Journals, LLC
external identifiers
  • pmid:26416425
  • wos:000366111900070
  • scopus:84946893392
ISSN
1949-2553
DOI
10.18632/oncotarget.5771
language
English
LU publication?
yes
id
fdc48a56-2ced-473c-a828-28f4afae9ae0 (old id 8034584)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26416425?dopt=Abstract
date added to LUP
2015-10-03 13:03:17
date last changed
2017-11-12 03:44:38
@article{fdc48a56-2ced-473c-a828-28f4afae9ae0,
  abstract     = {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.},
  author       = {Denisova, Evgeniya and Heidenreich, Barbara and Nagore, Eduardo and Rachakonda, P Sivaramakrishna and Hosen, Ismail and Akrap, Ivana and Traves, Víctor and García-Casado, Zaida and López-Guerrero, José Antonio and Requena, Celia and Sanmartin, Onofre and Serra-Guillén, Carlos and Llombart, Beatriz and Guillén, Carlos and Ferrando, Jose and Gimeno, Enrique and Nordheim, Alfred and Hemminki, Kari and Kumar, Rajiv},
  issn         = {1949-2553},
  language     = {eng},
  number       = {34},
  pages        = {35922--35930},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Frequent DPH3 promoter mutations in skin cancers.},
  url          = {http://dx.doi.org/10.18632/oncotarget.5771},
  volume       = {6},
  year         = {2015},
}