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
Publisher: Impact Journals
Year of publication: 2017
No. of pages: 10
Publication type: Article
ISSN: 1949-2553