Analysis of Genomic Alteration in Primary Central Nervous System Lymphoma and the Expression of Some Related Genes

Zhou, Yangying; Liu, Wei; Xu, Zhijie; Zhu, Hong; Xiao, Desheng; Su, Weiping; Zeng, Ruolan; Feng, Yuhua; Duan, Yumei; Zhou, Jianhua; Zhong, Meizuo

doi:10.1016/j.neo.2018.08.012

Cited by 49 publications

(46 citation statements)

References 78 publications

(85 reference statements)

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“…1,79 Isolated MYC, BCL2 or BCL6 rearrangements are uncommon, but have been reported at low frequency. 80 Zhou et al 81 meticulously categorised mutations encountered in DLBCL-CNS into eight cellular pathways. NF-kB, B-cell receptor signalling, epigenetic modulation and apoptosis regulation are involved.…”

Section: Immunophenotypementioning

confidence: 99%

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Diffuse large B-cell lymphoma variants: an update

et al. 2020

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Section: Immunophenotypementioning

confidence: 99%

“…NF-kB, B-cell receptor signalling, epigenetic modulation and apoptosis regulation are involved. 78,81 PIM1, MYD88, CD79B, and CDKN2A are among the most common genes mutated, some of which can be attributed to somatic hypermutation. 82 TP53 mutations have been identified in 27-37% of cases.…”

Section: Immunophenotypementioning

confidence: 99%

Diffuse large B-cell lymphoma variants: an update

et al. 2020

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“…The results suggest that PIM1 is mainly expressed in the nucleus, while MYD88 staining is largely cytoplasmic, with almost no nuclear staining. Compared with the control group, the positive expression rates of PIM1 and MYD88 were higher in PCNSL, and their expression levels were positively correlated (r = 0.581, P = 2.0 × 10 -6 ) [19].…”

Section: Survival Analysis Based On Expression Of High-frequency Genesmentioning

confidence: 80%

Genetic Map of Relapsed and Refractory Diffuse Large B-cell Lymphoma: A Systemic Review and Association Analysis

Gao¹,

Tian²,

Wang³

et al. 2020

Preprint

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Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL). In recent years, a deeper understanding of the genetic subtypes of diffuse large B lymphoma has been reached, and these advances have also been applied to research on relapsed and refractory diffuse large B-cell lymphoma (RRDLBCL). We screened 1495 documents, compiled the whole-exome sequencing data of several studies, formed a data set including 92 observations, and performed association analysis on the high-frequency mutations among them. The most common mutations in the data set include TTN (34/92, 37.0%), KMT2D (29/92, 31.5%), TP53 (25/92, 27.2%), IGLL5 (25/92, 27.2%), CREBBP (21 /92, 22.8%), BCL2 (21/92, 22.8%), MYD88 (20/92, 21.7%), and SOCS1 (19/92, 20.7%). Among these, CREBBP, KMT2D, and BCL2 have a strong association with each other, and SOCS1 has a strong association with genes such as ACTB, CIITA, and GNA13. There is also a strong association between SOCS1 and STAT6. Though TP53 and MYD88 lack significant associations with most genes, the association between MYD88 and PIM1 is significant. Through SOM clustering and expression-level analysis of common gene mutations, we believe that RRDLBCL can be divided into four main types: (1) JAK-STAT-related type, including STAT6, SOCS1, ITPKB, CIITA, and B2M. The expression lineage is similar to PMBL and cHL. (2) EZB type: BCL2 and EZHZ are the main types of mutations. Epigenetic mutations such as KMT2D and CREBBP are more common in this type, and are often accompanied by BCL2 mutations. (3) MCD type, including MYD88, CD79B and PIM1. These genes are involved in the BCR signaling pathway and related pathways, and are connected by the common NF-κB pathway. (4) Undefined type (Sparse Mutation type). These patients are mainly individuals with sparse mutations, including some patients with TP53 mutations (30.3%, 10/33), but who generally lack characteristic mutations. Among the common gene mutations, the expression changes in BCL2, PIM1, STAT6, ITPKB, and GNA13 have more significant prognostic significance. We also reviewed the literature from recent years concerning the previously mentioned common gene mutations.

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“…NF-κB signaling was also found hyper-activated in immune-rich PCNSL. Previous studies have shown that MYD88 gene mutations are highly prevalent and support lymphoma growth through NF-κB signaling in PCNSL [10][11][12][13]. It would hence be reasonable to co-assess the genomic and immune phenotypic statuses of PCNSL to propose combined ibrutinib/ICI therapies to immune rich/MYD88-mutated PCNSL patients (ongoing trial NCT03770416).…”

Section: Discussionmentioning

confidence: 99%

“…Significant efforts have been devoted to the identification of common genetic alterations and activating oncogenic signaling in PCNSL [7][8][9][10][11][12][13][14]. These alterations mainly involve Nuclear factor-kappa B (NF-κB), B cell receptor (BCR), Toll-like receptors (TLR), Mitogen-activated protein kinase (MAPK) signaling, the DNA damage response, apoptosis, and cell cycle control.…”

Section: Introductionmentioning

confidence: 99%

The immune landscape of primary central nervous system diffuse large B cell lymphoma

Alame

Cornillot

Cacheux

et al. 2020

Preprint

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Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is a rare and aggressive entity that resides in an immune-privileged site. The tumor microenvironment (TME) and the disruption of the immune surveillance influence lymphoma pathogenesis and immunotherapy resistance. Despite growing knowledge on heterogeneous therapeutic responses, no comprehensive description of the PCNSL TME is available. We investigated the immune subtypes of PCNSL and their association with molecular signaling and survival. Bulk mRNA-sequencing (n=20) and microarray (n=34) data were exploited to identify three immune subtypes of PCNSL: immune-rich, poor, and intermediate. The immune-rich subtype was associated to better survival and characterized by hyper-activation of STAT3 signaling and inflammatory signaling, e.g., IFNγ and TNF-α, resembling the hot subtype described in primary testicular lymphoma and solid cancer. WNT/β-catenin, HIPPO, and NOTCH signaling were hyper-activated in the immune-poor subtype. HLA down-modulation was clearly associated with a low or intermediate immune infiltration and the absence of T-cell activation. Moreover, HLA class I down-regulation was also correlated with worse survival with implications on immune-intermediate PCNSL that frequently feature reduced HLA expression. A ligand-receptor intercellular network revealed high expression of two immune checkpoints, i.e., CTLA-4/CD86 and TIM-3/LAGLS9. Immunohistopathology and digital imaging showed that TIM-3 and galectin-9 proteins were clearly upregulated in PCNSL. Altogether, our study reveals that patient stratification according to immune subtypes, HLA status, and immune checkpoint molecule quantification should be considered prior to immune checkpoint inhibitor therapy. Moreover, TIM-3 protein should be considered an axis for future therapeutic development.

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Analysis of Genomic Alteration in Primary Central Nervous System Lymphoma and the Expression of Some Related Genes

Cited by 49 publications

References 78 publications

Diffuse large B-cell lymphoma variants: an update

Diffuse large B-cell lymphoma variants: an update

Genetic Map of Relapsed and Refractory Diffuse Large B-cell Lymphoma: A Systemic Review and Association Analysis

The immune landscape of primary central nervous system diffuse large B cell lymphoma

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