The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies

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 exo...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Martin, Daniel, Abba, Martín Carlos, Molinolo, Alfredo A., Vitale-Cross, Lynn, Wang, Zhiyong., Zaida, Moraima, Delic, Naomi C., Samuels, Yardena, Lyons, J. Guy, Gutkind, J. Silvio
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Ciencias Médicas
Cancer
Exome
HNSCC
RNAseq
Sequencing
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85309
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85309
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Cancer
Exome
HNSCC
RNAseq
Sequencing
spellingShingle Ciencias Médicas
Cancer
Exome
HNSCC
RNAseq
Sequencing
Martin, Daniel
Abba, Martín Carlos
Molinolo, Alfredo A.
Vitale-Cross, Lynn
Wang, Zhiyong.
Zaida, Moraima
Delic, Naomi C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies
topic_facet Ciencias Médicas
Cancer
Exome
HNSCC
RNAseq
Sequencing
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.
format Articulo
Articulo
author Martin, Daniel
Abba, Martín Carlos
Molinolo, Alfredo A.
Vitale-Cross, Lynn
Wang, Zhiyong.
Zaida, Moraima
Delic, Naomi C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
author_facet Martin, Daniel
Abba, Martín Carlos
Molinolo, Alfredo A.
Vitale-Cross, Lynn
Wang, Zhiyong.
Zaida, Moraima
Delic, Naomi C.
Samuels, Yardena
Lyons, J. Guy
Gutkind, J. Silvio
author_sort Martin, Daniel
title The head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies
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 head and neck cancer cell oncogenome: a platform for the development of precision molecular therapies
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/85309
work_keys_str_mv AT martindaniel theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT abbamartincarlos theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT molinoloalfredoa theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT vitalecrosslynn theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT wangzhiyong theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT zaidamoraima theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT delicnaomic theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT samuelsyardena theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT lyonsjguy theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT gutkindjsilvio theheadandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT martindaniel headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT abbamartincarlos headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT molinoloalfredoa headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT vitalecrosslynn headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT wangzhiyong headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT zaidamoraima headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT delicnaomic headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT samuelsyardena headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT lyonsjguy headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
AT gutkindjsilvio headandneckcancercelloncogenomeaplatformforthedevelopmentofprecisionmoleculartherapies
bdutipo_str Repositorios
_version_ 1764820489236119554

Ejemplares similares