The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies

Autores
Martin, Daniel; Abba, Martín Carlos; Molinolo, Alfredo; Vitale Cross, Lynn; Wang, Zhiyong; Zaida, Moraima; Delic, Noami C.; Samuels, Yardena; Lyons, J. Guy; Gutkind, J. Silvio
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.
Fil: Martin, Daniel. National Institutes of Health. Bethesda; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Molinolo, Alfredo. National Institutes of Health. Bethesda; Estados Unidos
Fil: Vitale Cross, Lynn. National Institutes of Health. Bethesda; Estados Unidos
Fil: Wang, Zhiyong. National Institutes of Health. Bethesda; Estados Unidos
Fil: Zaida, Moraima. National Institutes of Health. Bethesda; Estados Unidos
Fil: Delic, Noami C.. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; Australia
Fil: Samuels, Yardena. The Weizmann Institute of Science. Rehovot; Israel
Fil: Lyons, J. Guy. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; Australia
Fil: Gutkind, J. Silvio. National Institutes of Health. Bethesda; Estados Unidos
Materia
Head
Neck
Oncogenomics
Cancer Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/32984
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular TherapiesMartin, DanielAbba, Martín CarlosMolinolo, AlfredoVitale Cross, LynnWang, ZhiyongZaida, MoraimaDelic, Noami C.Samuels, YardenaLyons, J. GuyGutkind, J. SilvioHeadNeckOncogenomicsCancer Cellshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.Fil: Martin, Daniel. National Institutes of Health. Bethesda; Estados UnidosFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Molinolo, Alfredo. National Institutes of Health. Bethesda; Estados UnidosFil: Vitale Cross, Lynn. National Institutes of Health. Bethesda; Estados UnidosFil: Wang, Zhiyong. National Institutes of Health. Bethesda; Estados UnidosFil: Zaida, Moraima. National Institutes of Health. Bethesda; Estados UnidosFil: Delic, Noami C.. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; AustraliaFil: Samuels, Yardena. The Weizmann Institute of Science. Rehovot; IsraelFil: Lyons, J. Guy. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; AustraliaFil: Gutkind, J. Silvio. National Institutes of Health. Bethesda; Estados UnidosOncotarget Inc.2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32984Martin, Daniel; Abba, Martín Carlos; Molinolo, Alfredo; Vitale Cross, Lynn; Wang, Zhiyong; et al.; The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies; Oncotarget Inc.; Oncotarget; 5; 9-2014; 8906-89231949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.2417info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=2417&path[]=5175info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:29Zoai:ri.conicet.gov.ar:11336/32984instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:29.573CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
title The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
spellingShingle The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
Martin, Daniel
Head
Neck
Oncogenomics
Cancer Cells
title_short The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
title_full The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
title_fullStr The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
title_full_unstemmed The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
title_sort The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies
dc.creator.none.fl_str_mv Martin, Daniel
Abba, Martín Carlos
Molinolo, Alfredo
Vitale Cross, Lynn
Wang, Zhiyong
Zaida, Moraima
Delic, Noami C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
author Martin, Daniel
author_facet Martin, Daniel
Abba, Martín Carlos
Molinolo, Alfredo
Vitale Cross, Lynn
Wang, Zhiyong
Zaida, Moraima
Delic, Noami C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
author_role author
author2 Abba, Martín Carlos
Molinolo, Alfredo
Vitale Cross, Lynn
Wang, Zhiyong
Zaida, Moraima
Delic, Noami C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Head
Neck
Oncogenomics
Cancer Cells
topic Head
Neck
Oncogenomics
Cancer Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.
Fil: Martin, Daniel. National Institutes of Health. Bethesda; Estados Unidos
Fil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina
Fil: Molinolo, Alfredo. National Institutes of Health. Bethesda; Estados Unidos
Fil: Vitale Cross, Lynn. National Institutes of Health. Bethesda; Estados Unidos
Fil: Wang, Zhiyong. National Institutes of Health. Bethesda; Estados Unidos
Fil: Zaida, Moraima. National Institutes of Health. Bethesda; Estados Unidos
Fil: Delic, Noami C.. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; Australia
Fil: Samuels, Yardena. The Weizmann Institute of Science. Rehovot; Israel
Fil: Lyons, J. Guy. University of Sydney. Camperdown; Australia. Royal Prince Alfred Hospital. Camperdown; Australia
Fil: Gutkind, J. Silvio. National Institutes of Health. Bethesda; Estados Unidos
description The recent elucidation of the genomic landscape of head and neck squamous cell carcinoma (HNSCC) has provided a unique opportunity to develop selective cancer treatment options. These efforts will require the establishment of relevant HNSCC models for preclinical testing. Here, we performed full exome and transcriptome sequencing of a large panel of HNSCC-derived cells from different anatomical locations and human papillomavirus (HPV) infection status. These cells exhibit typical mutations in TP53, FAT1, CDK2NA, CASP8, and NOTCH1, and copy number variations (CNVs) and mutations in PIK3CA, HRAS, and PTEN that reflect the widespread activation of the PI3K-mTOR pathway. SMAD4 alterations were observed that may explain the decreased tumor suppressive effect of TGF-β in HNSCC. Surprisingly, we identified HPV+ HNSCC cells harboring TP53 mutations, and documented aberrant TP53 expression in a subset of HPV+ HNSCC cases. This analysis also revealed that most HNSCC cells harbor multiple mutations and CNVs in epigenetic modifiers (e.g., EP300, CREBP, MLL1, MLL2, MLL3, KDM6A, and KDM6B) that may contribute to HNSCC initiation and progression. These genetically-defined experimental HNSCC cellular systems, together with the identification of novel actionable molecular targets, may now facilitate the pre-clinical evaluation of emerging therapeutic agents in tumors exhibiting each precise genomic alteration.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/32984
Martin, Daniel; Abba, Martín Carlos; Molinolo, Alfredo; Vitale Cross, Lynn; Wang, Zhiyong; et al.; The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies; Oncotarget Inc.; Oncotarget; 5; 9-2014; 8906-8923
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32984
identifier_str_mv Martin, Daniel; Abba, Martín Carlos; Molinolo, Alfredo; Vitale Cross, Lynn; Wang, Zhiyong; et al.; The Head and Neck Cancer Cell Oncogenome: A Platform for the Development of Precision Molecular Therapies; Oncotarget Inc.; Oncotarget; 5; 9-2014; 8906-8923
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.2417
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=2417&path[]=5175
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oncotarget Inc.
publisher.none.fl_str_mv Oncotarget Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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