| Literature DB >> 34478526 |
Ruben A L de Groen1, Ronald van Eijk2, Stefan Böhringer3, Tom van Wezel2, Richard Raghoo4, Dina Ruano2, Patty M Jansen2, Inge Briaire-de Bruijn2, Fleur A de Groot1, Karin Kleiverda2, Liane Te Boome5, Valeska Terpstra6, Henriette Levenga7, Alina Nicolae8, Eduardus F M Posthuma5, Isabelle Focke-Snieders9, Lizan Hardi10, Wietske C E den Hartog11, Lara H Bohmer12, Pancras C W Hogendoorn2, Anke van den Berg13, Arjan Diepstra13, Marcel Nijland14, Pieternella J Lugtenburg15, Marie José Kersten16,17,18, Steven T Pals16,18,19, Hendrik Veelken1, Judith V M G Bovée2, Arjen H G Cleven2, Joost S P Vermaat1.
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).Entities:
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Year: 2021 PMID： 34478526 PMCID： PMC8679674 DOI： 10.1182/bloodadvances.2021005215
Source DB: PubMed Journal: Blood Adv ISSN： 2473-9529