Mutational landscape of aggressive cutaneous squamous cell carcinoma

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...

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Main Author: Saade, Rami E. (author)
Other Authors: Pickering, Curtis R. (author), Zhou, Jane H. (author), Drummond, Jennifer A. (author), Curry, Jonathan (author)
Format: article
Published: 2017
Online Access:http://hdl.handle.net/10725/6148
http://dx.doi.org/ 10.1158/1078-0432.CCR-14-1768
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://clincancerres.aacrjournals.org/content/early/2014/10/10/1078-0432.CCR-14-1768.full-text.pdf
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author Saade, Rami E.
author2 Pickering, Curtis R.
Zhou, Jane H.
Drummond, Jennifer A.
Curry, Jonathan
author2_role author
author
author
author
author_facet Saade, Rami E.
Pickering, Curtis R.
Zhou, Jane H.
Drummond, Jennifer A.
Curry, Jonathan
author_role author
dc.creator.none.fl_str_mv Saade, Rami E.
Pickering, Curtis R.
Zhou, Jane H.
Drummond, Jennifer A.
Curry, Jonathan
dc.date.none.fl_str_mv 2017-09-07T06:20:56Z
2017-09-07T06:20:56Z
2017-09-07
dc.identifier.none.fl_str_mv 1557-3265
http://hdl.handle.net/10725/6148
http://dx.doi.org/ 10.1158/1078-0432.CCR-14-1768
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.
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://clincancerres.aacrjournals.org/content/early/2014/10/10/1078-0432.CCR-14-1768.full-text.pdf
dc.language.none.fl_str_mv en
dc.relation.none.fl_str_mv Clinical Cancer Research
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.title.none.fl_str_mv Mutational landscape of aggressive cutaneous squamous cell carcinoma
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description 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.
eu_rights_str_mv openAccess
format article
id LAURepo_56433afa31f50be5e62cfb2e2e99950f
identifier_str_mv 1557-3265
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.
language_invalid_str_mv en
network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/6148
publishDate 2017
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repository.name.fl_str_mv
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spelling Mutational landscape of aggressive cutaneous squamous cell carcinomaSaade, Rami E.Pickering, Curtis R.Zhou, Jane H.Drummond, Jennifer A.Curry, JonathanPurpose: 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.PublishedN/A2017-09-07T06:20:56Z2017-09-07T06:20:56Z2017-09-07Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1557-3265http://hdl.handle.net/10725/6148http://dx.doi.org/ 10.1158/1078-0432.CCR-14-1768Pickering, 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.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://clincancerres.aacrjournals.org/content/early/2014/10/10/1078-0432.CCR-14-1768.full-text.pdfenClinical Cancer Researchinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/61482021-03-19T10:00:48Z
spellingShingle Mutational landscape of aggressive cutaneous squamous cell carcinoma
Saade, Rami E.
status_str publishedVersion
title Mutational landscape of aggressive cutaneous squamous cell carcinoma
title_full Mutational landscape of aggressive cutaneous squamous cell carcinoma
title_fullStr Mutational landscape of aggressive cutaneous squamous cell carcinoma
title_full_unstemmed Mutational landscape of aggressive cutaneous squamous cell carcinoma
title_short Mutational landscape of aggressive cutaneous squamous cell carcinoma
title_sort Mutational landscape of aggressive cutaneous squamous cell carcinoma
url http://hdl.handle.net/10725/6148
http://dx.doi.org/ 10.1158/1078-0432.CCR-14-1768
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://clincancerres.aacrjournals.org/content/early/2014/10/10/1078-0432.CCR-14-1768.full-text.pdf