Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets
| Autor: | Juan F. García, Beatriz Sanchez-Espiridion, Fernando Burgos, Mónica Estévez, Elena Mata, Javier Menárguez, Ana M. Martín-Moreno, Carlos Montalbán, Miguel A. Piris, Mariano Provencio, Ignacio Varela, Margarita Sánchez-Beato, Eva C. Diaz, Maria J Mestre, Antonio Díaz-López, Carlos Santonja |
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| Přispěvatelé: | UAM. Departamento de Medicina, Universidad de Cantabria, Ministerio de Economía y Competitividad (España), Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, European Commission |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Therapeutic target Medicina Disease 03 medical and health sciences 0302 clinical medicine Internal medicine hemic and lymphatic diseases B-cell receptor medicine High prevalence business.industry Cancer Bcr signaling medicine.disease Mutational analysis humanities BCL10 Lymphoma 030104 developmental biology BTK 030220 oncology & carcinogenesis Hodgkin lymphoma business Research Paper |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM instname Oncotarget, 2017, Vol. 8, (No. 67), pp: 111386-111395 Digital.CSIC. Repositorio Institucional del CSIC UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) Oncotarget Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| Popis: | Mata et al. 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. This work was supported by grants from the Plan Nacional de I+D+I co-financed by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), PI12/1832, RTICC RD06/0020/0107, PI14/00221, CIBER de Cancer, PIE15/0081 and PI16/01294, the Spanish Association for Cancer Research (AECC), and by funds of the U.T M.D. Anderson Cancer Center. MSB currently holds a Miguel Servet contract (CP11/00018 and CPII16/00024) from the ISCIII- MINECO-AES-FEDER (P.N.I+D+I 2008-2011), Spain. |
| Databáze: | OpenAIRE |
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