Mutational landscape of immune surveillance genes in diffuse large B-cell lymphoma

Nesic, Marijana; El‐Galaly, Tarec Christoffer; Bøgsted, Martin; Pedersen, Inge Søkilde; Dybkær, Karen

doi:10.1080/17474086.2020.1755958

Cited by 3 publications

(12 citation statements)

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“…From a curated list of 58 genes encompassing all major immune surveillance pathways [ 21 , 41 , 42 ], genetic variants were detected in 48 out of 58 genes in our dataset. A total of 242 somatic variants were detected in the 48 affected immune surveillance genes, which after filtering for quality, resulted in 147 nonsynonymous, nonsense, small frameshifts, and splice variants in a total of 36 immune surveillance genes included in downstream analysis.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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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Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…These signals are generated by cells in the lymph nodes. In B-cell non-Hodgkin's lymphoma (B-NHL), the cancer cells are similar to the normal B cells, and they associate the immune inflammatory response with the potential of malignant clone for growth [2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms in NLRP3 Inflammasome-Associated Genes in Patients with B-Cell Non-Hodgkin’s Lymphoma

Liu¹,

Zhang²,

Jing³

et al. 2021

JIR

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“…In addition, loss-of-function mutations of the B2M gene are commonly observed in the DLBCL, leading to deficiency of MHC-I molecule expression and reduced immunogenicity [49]. Likewise, MHC-II antigen-presentation is pivotal for adaptive immune response, which in the malignant situation can be disturbed by different genetic mechanisms [50]. Genetic studies revealed that one of the main mechanisms responsible for the loss of MHC-II expression is the inactivation of the CIITA transactivator through somatic mutations and gene fusions with PD-L1 and PD-L2 genes [51].…”

Section: (A) Avoiding Immune Recognitionmentioning

confidence: 99%

“…A systematic literature search was conducted to identify genes involved in immune surveillance pathways and obtain gene mutation frequencies of immune surveillance genes in DLBCL patients. Fifty-eight genes related to immune surveillance pathways were identified to be either mutated or aberrantly expressed in DLBCL patients [50].…”

Section: Paper Imentioning

confidence: 99%

“…For each gene, the gene mutation frequency was calculated by summing the mutated samples in individual studies and divide by the total number of clinical samples from all included studies (Figure 11) [50]. The highest gene mutation frequencies were observed for PIM1, CREBBP, and TNFRSF14, yet both gene mutation frequency and the number of detected genes varied among studies [50]. The cohort sizes of included studies varied noteworthy from 7-1001 clinical samples.…”

Section: Paper Imentioning

confidence: 99%

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The role of genetic alterations and immune surveillance in diffuse large B-cell lymphoma

Nesic¹

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Mutational landscape of immune surveillance genes in diffuse large B-cell lymphoma

Cited by 3 publications

References 102 publications

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

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

Genetic Polymorphisms in NLRP3 Inflammasome-Associated Genes in Patients with B-Cell Non-Hodgkin’s Lymphoma

The role of genetic alterations and immune surveillance in diffuse large B-cell lymphoma

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