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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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Mutational Evolution in Relapsed Diffuse Large B-Cell Lymphoma.

Marcel Nijland1, Annika Seitz2, Martijn Terpstra3

  • 1Department of Hematology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands. m.nijland@umcg.nl.

Cancers
|November 23, 2018
PubMed
Summary

Genomic analysis of diffuse large B-cell lymphoma (DLBCL) reveals modest tumor evolution between primary and relapse biopsies. New mutations and potential therapy resistance genes were identified, impacting future treatment strategies.

Keywords:
diffuse large B-cell lymphomaevolutionfresh frozen paraffin embeddedheterogeneitymutationsrelapse

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Area of Science:

  • Genomics
  • Cancer Biology
  • Hematology

Background:

  • Current genomic models for diffuse large B-cell lymphoma (DLBCL) rely on single biopsies, potentially missing tumor heterogeneity.
  • Understanding the mutational evolution of DLBCL over time is crucial for effective treatment.

Purpose of the Study:

  • To assess mutational evolution in DLBCL using paired primary and relapse tumor biopsies.
  • To identify gene mutations associated with therapy resistance in relapsed DLBCL.

Main Methods:

  • Whole exome sequencing was performed on 14 paired formalin-fixed, paraffin-embedded DLBCL biopsies from 6 patients.
  • Analysis focused on comparing mutations between primary and relapse samples, particularly in patients treated with R-CVP chemotherapy.

Main Results:

  • A minority of primary mutations were lost, while relapsed samples showed a mild increase in mutations compared to primary tumors.
  • 264 potential therapy resistance genes were identified, including tyrosine kinases, glycoproteins, and JAK-STAT pathway genes.
  • Specific genes like PIM1, SOCS1, and MYC, linked to treatment failure risk, were noted.

Conclusions:

  • DLBCL exhibits modest temporal heterogeneity with acquired mutations during relapse.
  • Identified genes associated with therapy resistance may inform treatment decisions and novel drug development.
  • This study highlights the importance of considering tumor evolution in DLBCL management.