Tracking the Genetic Susceptibility Background of B-Cell Non-Hodgkin’s Lymphomas from Genome-Wide Association Studies

Abstract

B-cell non-Hodgkin’s lymphoma (NHL) risk associations had been mainly attributed to family history of the disease, inflammation, and immune components including human leukocyte antigen (HLA) genetic variations. Nevertheless, a broad range of genome-wide association studies (GWAS) have shed light into the identification of several genetic variants presumptively associated with B-cell NHL etiologies, survival or shared genetic risk with other diseases. The present review aims to overview HLA structure and diversity and summarize the evidence of genetic variations, by GWAS, on five NHL subtypes (diffuse large B-cell lymphoma DLBCL, follicular lymphoma FL, chronic lymphocytic leukemia CLL, marginal zone lymphoma MZL, and primary central nervous system lymphoma PCNSL). Evidence indicates that the HLA zygosity status in B-cell NHL might promote immune escape and that genome-wide significance variants can give biological insight but also potential therapeutic markers such as WEE1 in DLBCL. However, additional studies are needed, especially for non-DLBCL, to replicate the associations found to date.

Phosphoproteome analysis of cerebrospinal fluid extracellular vesicles in primary central nervous system lymphoma

“…MARCS, a filamentous (F) actin cross-linking protein, binds calmodulin, actin and synapsin and is closely related to the immunochemotherapy resistance and prognosis of DLBCL. 32,33 It is interesting to note that the loss of HLA is a mechanism for immune escape and also the symbol of poor prognosis and high risk of relapse in DLBCL, 34 whereas in our results, the relative intensity of HLA-A in CSF EV samples from PCNSL patients is higher than that in the control, indicating stable, even enhanced, T-cell immunity in PCNSL. NPM is also reported as a prognostic predictor of primary DLBCL in the CNS.…”

Meta-Analysis of MS-Based Proteomics Studies Indicates Interferon Regulatory Factor 4 and Nucleobindin1 as Potential Prognostic and Drug Resistance Biomarkers in Diffuse Large B Cell Lymphoma

“…DLBCL, like other cancers, could be the result of an imbalance in immune control. Previous research has found that genetic background (such as HLA zygosity status) [121], autoimmune diseases, and viral infections all increase the risk of DLBCL [107,122]. Furthermore, genetic factors influence the distribution and behavior of immune cells in the tumor microenvironment [123].…”

The TiHoCL panel for canine lymphoma: a feasibility study integrating functional genomics and network biology approaches for comparative oncology targeted NGS panel design

“…As in NHL and other canine cancers, increased risk, poor prognosis, and resistance to treatment in CL are very likely related to the genetic background of the host (19)(20)(21)(22)(23)(24)(25)(26). Candidate gene, linkage and genome-wide association studies (GWASs) have revealed multiple genetic variants associated with NHL (25, [27][28][29][30]. Specifically, genetic alterations associated with NHL include both single nucleotide variants and large rearrangements that place genes under the control of promoters and enhancers that are typically only active in the lymphocytes, leading to dysregulation of genes in pathways involving immune function, cell cycle, apoptosis, DNA repair, and carcinogen metabolism (31)(32)(33).…”