2. Academic Validation
  3. Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets

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

  • Oncotarget. 2017 Nov 30;8(67):111386-111395. doi: 10.18632/oncotarget.22799.
Elena Mata 1,  Antonio Díaz-López 1,  Ana M Martín-Moreno 1,  Margarita Sánchez-Beato 2,  Ignacio Varela 3,  María J Mestre 4,  Carlos Santonja 5,  Fernando Burgos 6,  Javier Menárguez 7,  Mónica Estévez 8,  Mariano Provencio 2,  Beatriz Sánchez-Espiridión 9,  Eva Díaz 1,  Carlos Montalbán 8,  Miguel A Piris 5,  Juan F García 1
Affiliations

Affiliations

  • 1 Department of Pathology and Translational Research, MD Anderson Cancer Center Madrid, Madrid, Spain.
  • 2 Lymphoma Research Group, Medical Oncology Department, Instituto Investigación Sanitaria Puerta de Hierro (IDIPHIM), Madrid, Spain.
  • 3 Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (CSIC, Universidad de Cantabria), Santander, Spain.
  • 4 Department of Pathology, Hospital Universitario de Móstoles, Madrid, Spain.
  • 5 Department of Pathology, Fundación Jiménez Díaz, Madrid, Spain.
  • 6 Department of Pathology, Hospital Severo Ochoa, Madrid, Spain.
  • 7 Department of Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • 8 Department of Hematology, MD Anderson Cancer Center Madrid, Madrid, Spain.
  • 9 Department of Molecular Translational Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
PMID: 29340061 DOI: 10.18632/oncotarget.22799
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.

Keywords

B-cell receptor; BTK; Hodgkin lymphoma; mutational analysis; therapeutic target.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-18012
    99.62%, Btk Inhibitor
    Btk