ArticleBlood advances2021
Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 17 citations in OpenAlex.
- Molecular mechanisms of Epstein-Barr Virus in the pathogenesis of lymphomas and new opportunities for precision medicine.Discover oncology · 2026Review
- Interferon regulatory factor 8 expression and features in blastic plasmacytoid dendritic cell neoplasm and extranodal NK/T-cell lymphoma, nasal type.Histology and histopathology · 2025Article
- Clinical characteristics and molecular heterogeneity in Follicular lymphoma with extranodal involvement.Genome medicine · 2025Article
- IgM Immunohistochemical Expression is a Potential Risk Factor for Extracutaneous Dissemination in Patients With Primary Cutaneous Follicle Center Lymphoma.The American journal of surgical pathology · 2025Article
- Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment.Blood cancer journal · 2025Article
- Genomic and immune profiling of prognostic risk groups in IgM gammopathy reveals novel biomarkers beyondFrontiers in immunology · 2025Article
- Impact of genetic alterations on central nervous system progression of primary vitreoretinal lymphoma.Haematologica · 2024Article
- Real-world routine diagnostic molecular analysis for TP53 mutational status is recommended over p53 immunohistochemistry in B-cell lymphomas.Virchows Archiv : an international journal of pathology · 2024Article
- Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features.Blood advances · 2024Article
- The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.International journal of molecular sciences · 2024Article
- Article
- Differences in mutational signature of diffuse large B-cell lymphomas according to the primary organ.Cancer medicine · 2023Article
- Emerging entities: high-grade/large B-cell lymphoma with 11q aberration, large B-cell lymphoma with IRF4 rearrangement, and new molecular subgroups in large B-cell lymphomas. A report of the 2022 EA4HP/SH lymphoma workshop.Virchows Archiv : an international journal of pathology · 2023Review
- Primary Bone Lymphoma: A Review of the Literature with Emphasis on Histopathology and Histogenesis.Diseases (Basel, Switzerland) · 2023Review
- Pathological fracture due to primary bone lymphoma in a patient with a history of prostate cancer: A case report and review of literature.Frontiers in oncology · 2023Article
- Proposal of Diagnostic Approach of Periodontal Primary Non Hodgkin Lymphoma of Bone with Flow Cytometry as an Essential Diagnostic Component.Head and neck pathology · 2022Article
- Article
- Review
- Site-Specific Survival of Extra Nodal Diffuse Large B-Cell Lymphoma and Comparison With Gastrointestinal Diffuse Large B-Cell Lymphoma.Journal of hematology · 2022Article
- Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas.Virchows Archiv : an international journal of pathology · 2022Article
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Authors and funding
30 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin was determined by immunohistochemistry and gene-expression profiling (GEP) using (extended)-NanoString/Lymph2Cx analysis. Mutational profiles were identified with targeted next-generation deep sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCLs, were predominantly classified as GCB phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx revealed significantly different GEP clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P < .001). Expression levels of 23 genes of 2 different targeted GEP panels indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB exhibited a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes (ie, B2M, EZH2, IRF8, TNFRSF14) compared with NO-DLBCL-GCB (P = .031, P = .010, P = .047, and P = .003, respectively). PB-DLBCL, with its corresponding specific mutational profile, was significantly associated with a superior survival compared with equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P = .016). This study is the first to show that PB-DLBCL is characterized by a GCB phenotype, with a centrocyte-like GEP pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity, and its specific mutational landscape offers potential for targeted therapies (eg, EZH2 inhibitors).
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