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Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets
Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cH...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762329/ https://www.ncbi.nlm.nih.gov/pubmed/29340061 http://dx.doi.org/10.18632/oncotarget.22799 |
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author | Mata, Elena Díaz-López, Antonio Martín-Moreno, Ana M. Sánchez-Beato, Margarita Varela, Ignacio Mestre, María J. Santonja, Carlos Burgos, Fernando Menárguez, Javier Estévez, Mónica Provencio, Mariano Sánchez-Espiridión, Beatriz Díaz, Eva Montalbán, Carlos Piris, Miguel A. García, Juan F. |
author_facet | Mata, Elena Díaz-López, Antonio Martín-Moreno, Ana M. Sánchez-Beato, Margarita Varela, Ignacio Mestre, María J. Santonja, Carlos Burgos, Fernando Menárguez, Javier Estévez, Mónica Provencio, Mariano Sánchez-Espiridión, Beatriz Díaz, Eva Montalbán, Carlos Piris, Miguel A. García, Juan F. |
author_sort | Mata, Elena |
collection | PubMed |
description | Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors in vitro constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease. |
format | Online Article Text |
id | pubmed-5762329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57623292018-01-16 Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets Mata, Elena Díaz-López, Antonio Martín-Moreno, Ana M. Sánchez-Beato, Margarita Varela, Ignacio Mestre, María J. Santonja, Carlos Burgos, Fernando Menárguez, Javier Estévez, Mónica Provencio, Mariano Sánchez-Espiridión, Beatriz Díaz, Eva Montalbán, Carlos Piris, Miguel A. García, Juan F. Oncotarget Research Paper Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors in vitro constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease. Impact Journals LLC 2017-11-30 /pmc/articles/PMC5762329/ /pubmed/29340061 http://dx.doi.org/10.18632/oncotarget.22799 Text en Copyright: © 2017 Mata et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Mata, Elena Díaz-López, Antonio Martín-Moreno, Ana M. Sánchez-Beato, Margarita Varela, Ignacio Mestre, María J. Santonja, Carlos Burgos, Fernando Menárguez, Javier Estévez, Mónica Provencio, Mariano Sánchez-Espiridión, Beatriz Díaz, Eva Montalbán, Carlos Piris, Miguel A. García, Juan F. Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title_full | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title_fullStr | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title_full_unstemmed | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title_short | Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
title_sort | analysis of the mutational landscape of classic hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762329/ https://www.ncbi.nlm.nih.gov/pubmed/29340061 http://dx.doi.org/10.18632/oncotarget.22799 |
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