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Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets

Abstract: 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.

 Fuente: Oncotarget, 2017, Vol. 8, (No. 67), pp: 111386-111395

 Editorial: Impact Journals

 Año de publicación: 2017

 Nº de páginas: 10

 Tipo de publicación: Artículo de Revista

 ISSN: 1949-2553

Autoría

MATA, ELENA

DÍAZ LÓPEZ, ANTONIO

MARTÍN MORENO, ANA M.

SÁNCHEZ BEATO, MARGARITA

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.