dc.contributor.author |
Saade, Rami E. |
|
dc.contributor.author |
Pickering, Curtis R. |
|
dc.contributor.author |
Zhou, Jane H. |
|
dc.contributor.author |
Drummond, Jennifer A. |
|
dc.contributor.author |
Curry, Jonathan |
|
dc.date.accessioned |
2017-09-07T06:20:56Z |
|
dc.date.available |
2017-09-07T06:20:56Z |
|
dc.date.issued |
2017-09-07 |
|
dc.identifier.issn |
1557-3265 |
en_US |
dc.identifier.uri |
http://hdl.handle.net/10725/6148 |
|
dc.description.abstract |
Purpose: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal
disease. Very little is currently known about the mutations that drive aggressive cSCC.
Experimental Design: Whole exome sequencing was performed on 39 cases of aggressive cSCC
to identify driver genes and novel therapeutic targets. Significantly mutated genes were
identified with MutSig or complementary methods developed to specifically identify candidate
tumor suppressors based upon their inactivating mutation bias.
Results: Despite the very high mutational background caused by UV exposure, 23 candidate
drivers were identified including the well-known cancer-associated genes TP53, CDKN2A,
NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor
suppressors with putative links to cancer or differentiation, NOTCH2, PARD3 and RASA1, were
also identified as possible drivers in cSCC. KMT2C mutations were associated with poor
outcome and increased bone invasion.
Conclusions: The mutational spectrum of cSCC is similar to that of head and neck squamous cell
carcinoma and dominated by tumor suppressor genes. These results improve the foundation for
understanding this disease and should aid in identifying and treating aggressive cSCC. |
en_US |
dc.language.iso |
en |
en_US |
dc.title |
Mutational landscape of aggressive cutaneous squamous cell carcinoma |
en_US |
dc.type |
Article |
en_US |
dc.description.version |
Published |
en_US |
dc.author.school |
SAS |
en_US |
dc.author.idnumber |
200102768 |
en_US |
dc.author.department |
Natural Sciences |
en_US |
dc.description.embargo |
N/A |
en_US |
dc.relation.journal |
Clinical Cancer Research |
en_US |
dc.keywords |
Head and neck/oral cancers |
en_US |
dc.keywords |
Melanoma/skin cancers |
en_US |
dc.keywords |
Mutagenesis |
en_US |
dc.keywords |
Oncogenes |
en_US |
dc.keywords |
Suppressor genes |
en_US |
dc.keywords |
Somatic alterations and genetic and environmental risk factors |
en_US |
dc.keywords |
Cutaneous squamous cell carcinoma |
en_US |
dc.keywords |
cSCC |
en_US |
dc.keywords |
Genomics |
en_US |
dc.identifier.doi |
http://dx.doi.org/ 10.1158/1078-0432.CCR-14-1768 |
en_US |
dc.identifier.ctation |
Pickering, C. R., Zhou, J. H., Lee, J. J., Drummond, J. A., Peng, S. A., Saade, R. E., ... & Yu, J. (2014). Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clinical cancer research, clincanres-1768. |
en_US |
dc.author.email |
rami.saade@lau.edu.lb |
en_US |
dc.identifier.tou |
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php |
en_US |
dc.identifier.url |
http://clincancerres.aacrjournals.org/content/early/2014/10/10/1078-0432.CCR-14-1768.full-text.pdf |
en_US |
dc.author.affiliation |
Lebanese American University |
en_US |