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4 results on '"den Hartog, Wietske C.E."'

1. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, Ruben A.L., van Eijk, Ronald, Böhringer, Stefan, van Wezel, Tom, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-de Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., van den Berg, Anke, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie José, Pals, Steven T., Veelken, Hendrik, Bovée, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

Published
2021
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3. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, A. L., van Eijk, Ronald, Bohringer, Stefan, Wezel, Tom van, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-De Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., den Berg, Anke van, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie Jose, Pals, Steven T., Veelken, Hendrik, Bovee, Judith V.M.G., Cleven, Arjen H.G., Vermaat, Joost S.P., de Groen, A. L., van Eijk, Ronald, Bohringer, Stefan, Wezel, Tom van, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-De Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., den Berg, Anke van, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie Jose, Pals, Steven T., Veelken, Hendrik, Bovee, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

Published
2021

4. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, Ruben A.L., van Eijk, Ronald, Böhringer, Stefan, van Wezel, Tom, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-de Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., van den Berg, Anke, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie José, Pals, Steven T., Veelken, Hendrik, Bovée, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

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).

Published
2021
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