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Open Access 01-12-2021 | Diffuse Large B-Cell Lymphoma | Research

The mutational profile of immune surveillance genes in diagnostic and refractory/relapsed DLBCLs

Authors: Marijana Nesic, Mads Sønderkær, Rasmus Froberg Brøndum, Tarec Christoffer El-Galaly, Inge Søkilde Pedersen, Martin Bøgsted, Karen Dybkær

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid neoplasm among adults,and approximately 30–40% of patients will experience relapse while 5–10% will suffer from primary refractory disease caused by different mechanisms, including treatment-induced resistance. For refractory and relapsed DLBCL (rrDLBCL) patients, early detection and understanding of the mechanisms controlling treatment resistance are of great importance to guide therapy decisions. Here, we have focused on genetic variations in immune surveillance genes in diagnostic DLBCL (dDLBCL) and rrDLBCL patients to elaborate on the suitability of new promising immunotherapies.

Methods

Biopsies from 30 dDLBCL patients who did not progress or relapse during follow up and 17 rrDLBCL patients with refractory disease or who relapsed during follow up were analyzed by whole-exome sequencing, including matched individual germline samples to include only somatic genetic variants in downstream analysis of a curated list of 58 genes involved in major immune surveillance pathways.

Results

More than 70% of both dDLBCLs and rrDLBCLs harbored alterations in immune surveillance genes, but rrDLBCL tumor samples have a lower number of genes affected compared to dDLBCL tumor samples. Increased gene mutation frequencies in rrDLBCLs were observed in more than half of the affected immune surveillance genes than dDLBCLs.

Conclusion

Genetic variants in the antigen-presenting genes affect a higher number of rrDLBCL patients supporting an important role for these genes in tumor progression and development of refractory disease and relapse.

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Title: The mutational profile of immune surveillance genes in diagnostic and refractory/relapsed DLBCLs
Authors: Marijana Nesic
Mads Sønderkær
Rasmus Froberg Brøndum
Tarec Christoffer El-Galaly
Inge Søkilde Pedersen
Martin Bøgsted
Karen Dybkær
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08556-3

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