Whole-Genome/Exome Sequencing Uncovers Mutations and Copy Number Variations in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Zhu, Qiong; Wang, Jianchao; Zhang, Wenfang; Zhu, Weixing; Wu, Zai-Zeng; Chen, Yanping; Chen, Musheng; Zheng, Limei; Tang, Jianguo; Zhang, Sheng; Wang, Di; Wang, Xingfu; Chen, Gang

doi:10.3389/fgene.2022.878618

Cited by 10 publications

(11 citation statements)

References 47 publications

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“…A possible explanation of these contradictory findings lies in the fact that the frequency of genetic alterations encompassing PD-1 ligands in PCNSL appears to be much lower than the one initially reported [38 ▪▪ ,68,69]. In addition, recurrent deletion of HLA genes [38 ▪▪ ,68,69] and presence of multiple inhibitory receptors on T cells infiltrating PCNSL [70] might represent additional reasons why T cells unleashed upon PD-1 blockade did yield the expected benefit.…”

Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 94%

“…One of the major limitations of CAR-T cells therapy in PCNSL lies in the peculiar immunosuppressive tumour microenvironment (TME) leading to T cells exhaustion [69]; in this perspective, novel combination therapies with other agents, including checkpoint inhibitors, could potentially overcome the negative influence of TME and therefore increase antitumor efficacy of CAR-T cells. Moreover, combination with Ibrutinib might be investigated due to the encouraging data reported in CLL [84].…”

Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 99%

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New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

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Purpose of review Patients with relapsed/refractory primary central nervous system lymphoma (rrPCNSL) have poor prognosis, with a median survival after relapse of 6.8 months. In this review, we discuss the evolving landscape and the possible future directions related to this important unmet clinical need. Recent findings The modern two-phase approach for newly diagnosed PCNSL based on an induction using high-dose methotrexate (HD-MTX) combinations and a subsequent consolidation, has significantly improved the outcome in this setting. However, this strategy is able to cure more or less 50% of patients. rrPCNSL patients have a very poor prognosis with a reported 5-year overall survival of 18%. Late relapses (after third year) and use of high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) represent important factors associated with a better outcome in this setting. On the basis of the growing acquisition of knowledge on the molecular characteristics of PCNSL, the use of non-chemotherapeutic drugs such as bruton tyrosine kinase inhibitors (BTK-is), immunomodulatory drugs (IMiDs) and immune checkpoint blockers (ICBs) is increasing in the last years along with the introduction of novel approaches (CAR-T cells and blood--brain barrier disruption). However, despite high responses in some cases, durations are often short, translating in outcome results still unsatisfactory. Summary Treatment of rrPCNSL patients is challenging. As no standard of care exist in this setting, it is of paramount importance to acquire new knowledge related to this condition and start multidisciplinary collaboration in order to improve pts outcome.

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Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 94%

Section: Novel Approaches For Relapsed/refractory Primary Central Ner...mentioning

confidence: 99%

New hopes in relapsed refractory primary central nervous system lymphoma

Calimeri

Steidl

Fiore

et al. 2023

Current Opinion in Oncology

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“…Chromosomal abnormalities included copy number gains of 2q37, 3q12.3, 7q, 11q, 9p24.1 (affecting CD274/PD-L1(programmed death-ligand 1) and PDCD1LG2/PD-L2(programmed death-ligand 2) ), 18q21 and chromosome 12, copy number deletions of 6p21–22 [human leukocyte antigen (HLA) locus], 6q21, 8q12, 9p21.3 ( CDKN2A biallelic loss), 19p13 ( CDKN2D ), and translocations of IgH-BCL6 [ 2 ▪▪ , 8 ▪▪ , 35 ▪ , 36 , 37 ].…”

Section: Molecular Profiles and Gene Expression Signatures Of Primary...mentioning

confidence: 99%

“…Focus to the most important gene mutations in PCNSLs: PIM1 gene mutations are described in 25--100% of cases [ 8 ▪▪ , 16 , 35 ▪ , 46 – 48 ]. Zhou et al [ 46 ] have divided CNS-DLBCL into two groups CDP ( PIM1 and/or CD79B mutations) and non-CDP (without PIM1 and CD79B mutations) with better outcome (long-term survival) observed for CDP group after high-dose methotrexate-based polychemotherapy.…”

Section: Molecular Profiles and Gene Expression Signatures Of Primary...mentioning

confidence: 99%

Pathology and new insights in central nervous system lymphomas

Lebrun

Allard-Demoustiez

Salmon

2023

Current Opinion in Oncology

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Purpose of review Primary central nervous system lymphoma (PCNSL) is a rare central nervous system (CNS) malignancy, which represents a heterogenous group of tumors. Among PCNSL, diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) represents the most common tumor type. Multiomics studies have recently revealed the complex genomic landscape of these rare diseases. These findings lead to a potential new molecular and epigenetic classification. Recent findings Our review is focused on CNS-DLBCL in immunocompetent patients. CNS-DLBCL are derived from self-reactive/polyreactive precursor cells. An early molecular event such as MYD88 mutation leads to escape elimination of precursor cells, which, by a dysregulated GC reaction, acquire auto-/polyreactivity of the B-cell tumoral cells for antigens physiologically expressed in the CNS. Most of CNS-DLBCL tumor cells harbor a non-GCB, ABC-like immunophenotype associated with a late GC (exit) B-cells genotype by gene expression profiling. Various mechanisms of genetic alterations are involved in the pathogenesis of PCNSL, including point mutations [nonsomatic hypermutation (SHM), aberrant SHM (aSHM)], SHM/aSHM, chromosome copy gains or losses, and DNA hypermethylation. Constitutive NFκB activation plays a key role in lymphoma cell proliferation and survival by dysregulation of toll-like receptor (mutations of CARD11 and MYD88), BCR (CD79B), JAK-STAT, and NFκB signaling pathways. Summary Multiomics approaches have succeeded to substantially improve the understanding of the pathogenesis, as well as the molecular and epigenetic events in PCNSL. Challenges remain due to the obvious heterogeneity of CNS-DLBCL, and improvement is needed for their classification.

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“…MYD88 L265P , is an important oncogene for lymphoma [ 324 – 327 ]. With the advancement of high-throughput molecular technologies, it has been found that mutations in the MYD88 L265P gene are present in 55–88% of patients with PCNSL [ 132 , 328 – 331 ]. Moreover, the protein expression of MYD88 was significantly elevated in PCNSL patients in comparison to individuals with lymphadenitis (70.18% vs. 15%) [ 58 ].…”

Section: Prognostic Markers For Pcnslmentioning

confidence: 99%

Extranodal lymphoma: pathogenesis, diagnosis and treatment

Yang,

Xun,

et al. 2023

Mol Biomed

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Approximately 30% of lymphomas occur outside the lymph nodes, spleen, or bone marrow, and the incidence of extranodal lymphoma has been rising in the past decade. While traditional chemotherapy and radiation therapy can improve survival outcomes for certain patients, the prognosis for extranodal lymphoma patients remains unsatisfactory. Extranodal lymphomas in different anatomical sites often have distinct cellular origins, pathogenic mechanisms, and clinical manifestations, significantly influencing their diagnosis and treatment. Therefore, it is necessary to provide a comprehensive summary of the pathogenesis, diagnosis, and treatment progress of extranodal lymphoma overall and specifically for different anatomical sites. This review summarizes the current progress in the common key signaling pathways in the development of extranodal lymphomas and intervention therapy. Furthermore, it provides insights into the pathogenesis, diagnosis, and treatment strategies of common extranodal lymphomas, including gastric mucosa-associated lymphoid tissue (MALT) lymphoma, mycosis fungoides (MF), natural killer/T-cell lymphoma (nasal type, NKTCL-NT), and primary central nervous system lymphoma (PCNSL). Additionally, as PCNSL is one of the extranodal lymphomas with the worst prognosis, this review specifically summarizes prognostic indicators and discusses the challenges and opportunities related to its clinical applications. The aim of this review is to assist clinical physicians and researchers in understanding the current status of extranodal lymphomas, enabling them to make informed clinical decisions that contribute to improving patient prognosis.

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Whole-Genome/Exome Sequencing Uncovers Mutations and Copy Number Variations in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Cited by 10 publications

References 47 publications

New hopes in relapsed refractory primary central nervous system lymphoma

New hopes in relapsed refractory primary central nervous system lymphoma

Pathology and new insights in central nervous system lymphomas

Extranodal lymphoma: pathogenesis, diagnosis and treatment

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