دورية أكاديمية
Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype
| العنوان: | Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype |
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| المؤلفون: | Groen, R.A.L. de, Eijk, R. van, Bohringer, S., Wezel, T. van, Raghoo, R., Ruano, D., Jansen, P.M., Briaire-De Bruijn, I., Groot, F.A. de, Kleiverda, K., Boome, L. te, Terpstra, V., Levenga, H., Nicolae, A., Posthuma, E.F.M., Focke-Snieders, I., Hardi, L., Hartog, W.C.E. den, Bohmer, L.H., Hogendoorn, P.C.W., Berg, A. van den, Diepstra, A., Nijland, M., Lugtenburg, P.J., Kersten, M.J., Pals, S.T., Veelken, H., Bovee, J.V.M.G., Cleven, A.H.G., Vermaat, J.S.P. |
| المصدر: | Blood Advances |
| سنة النشر: | 2021 |
| المجموعة: | Leiden Repository (Leiden University) |
| الوصف: | 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 DLBCLwith 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)-Nano-String/Lymph2Cx analysis. Mutational profileswere identifiedwith 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) comparedwithNO-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). ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://ashpublications.org/bloodadvances/article-pdf/5/19/3760/1824825/advancesadv2021005215.pdfTest; lumc-id: 121241685; https://hdl.handle.net/1887/3263762Test |
| DOI: | 10.1182/bloodadvances.2021005215 |
| الإتاحة: | https://doi.org/10.1182/bloodadvances.2021005215Test https://hdl.handle.net/1887/3263762Test https://ashpublications.org/bloodadvances/article-pdf/5/19/3760/1824825/advancesadv2021005215.pdfTest |
| رقم الانضمام: | edsbas.B6D9B403 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/bloodadvances.2021005215 |
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