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

BMC Cancer

Rasmus Froberg Brøndum¹  Inge Søkilde Pedersen²  Mads Sønderkær³  Marijana Nesic⁴  Martin Bøgsted⁵  Tarec Christoffer El-Galaly⁵  Karen Dybkær⁵ 

[1] Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark;Department of Molecular Diagnostics, Aalborg, Denmark;Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark;Department of Molecular Diagnostics, Aalborg, Denmark;Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark;Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark;

关键词: Diagnostic DLBCL;    Refractory/relapsed DLBCL;    Immune surveillance;    MHC class I;    MHC class II;    Somatic mutations;    Gene;    Immunotherapy;   

DOI  :  10.1186/s12885-021-08556-3

来源: Springer

【 摘 要 】

BackgroundDiffuse 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.MethodsBiopsies 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.ResultsMore 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.ConclusionGenetic 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.

【 授权许可】

CC BY