TY - JOUR
T1 - Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets
AU - Mata, Elena
AU - Díaz-López, Antonio
AU - Martín-Moreno, Ana M.
AU - Sánchez-Beato, Margarita
AU - Varela, Ignacio
AU - Mestre, María J.
AU - Santonja, Carlos
AU - Burgos, Fernando
AU - Menárguez, Javier
AU - Estévez, Mónica
AU - Provencio, Mariano
AU - Sánchez-Espiridión, Beatriz
AU - Díaz, Eva
AU - Montalbán, Carlos
AU - Piris, Miguel A.
AU - García, Juan F.
N1 - Publisher Copyright:
© Mata et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - B-cell receptor
KW - BTK
KW - Hodgkin lymphoma
KW - Mutational analysis
KW - Therapeutic target
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U2 - 10.18632/oncotarget.22799
DO - 10.18632/oncotarget.22799
M3 - Article
C2 - 29340061
AN - SCOPUS:85038429755
SN - 1949-2553
VL - 8
SP - 111386
EP - 111395
JO - Oncotarget
JF - Oncotarget
IS - 67
ER -