1. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
- Author
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Mansouri, Larry, Noerenberg, Daniel, Young, Emma, Mylonas, Elena, Abdulla, Maysaa, Frick, Mareike, Asmar, Fazila, Ljungström, Viktor, Schneider, Markus, Yoshida, Kenichi, Skaftason, Aron, Pandzic, Tatjana, Gonzalez, Blanca, Tasidou, Anna, Waldhueter, Nils, Rivas-Delgado, Alfredo, Angelopoulou, Maria, Ziepert, Marita, Arends, Christopher-Maximilian, Couronne, Lucile, Lenze, Dido, Claudia, Baldus, Bastard, Christian, Okosun, Jessica, Fitzgibbon, Jude, Dörken, Bernd, Drexler, Hans G, Roos-Weil, Damien, Schmitt, Clemens A, Munch-Petersen, Helga D, Zenz, Thorsten, Hansmann, Martin-Leo, Strefford, Jonathan C, Enblad, Gunilla, Bernard, Olivier, Ralfkiaer, Elisabeth, Erlanson, Martin, Korkolopoulou, Penelope, Hultdin, Magnus, Papadaki, Theodora, Grønbæk, Kirsten, Lopez-Guillermo, Armando, Ogawa, Seishi, Küppers, Ralf, Stamatopoulos, Kostas, Stavroyianni, Niki, Kanellis, George, Rosenwald, Andreas, Campo, Elias, Amini, Rose-Marie, Ott, German, Vasslakopoulos, Theodoros P, Hummel, Michael, Rosenquist, Richard, Damm, Frederik, Mansouri, Larry, Noerenberg, Daniel, Young, Emma, Mylonas, Elena, Abdulla, Maysaa, Frick, Mareike, Asmar, Fazila, Ljungström, Viktor, Schneider, Markus, Yoshida, Kenichi, Skaftason, Aron, Pandzic, Tatjana, Gonzalez, Blanca, Tasidou, Anna, Waldhueter, Nils, Rivas-Delgado, Alfredo, Angelopoulou, Maria, Ziepert, Marita, Arends, Christopher-Maximilian, Couronne, Lucile, Lenze, Dido, Claudia, Baldus, Bastard, Christian, Okosun, Jessica, Fitzgibbon, Jude, Dörken, Bernd, Drexler, Hans G, Roos-Weil, Damien, Schmitt, Clemens A, Munch-Petersen, Helga D, Zenz, Thorsten, Hansmann, Martin-Leo, Strefford, Jonathan C, Enblad, Gunilla, Bernard, Olivier, Ralfkiaer, Elisabeth, Erlanson, Martin, Korkolopoulou, Penelope, Hultdin, Magnus, Papadaki, Theodora, Grønbæk, Kirsten, Lopez-Guillermo, Armando, Ogawa, Seishi, Küppers, Ralf, Stamatopoulos, Kostas, Stavroyianni, Niki, Kanellis, George, Rosenwald, Andreas, Campo, Elias, Amini, Rose-Marie, Ott, German, Vasslakopoulos, Theodoros P, Hummel, Michael, Rosenquist, Richard, and Damm, Frederik
- Abstract
We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIEaberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL., L.M., D.N., and E.Y. contributed equally to this study as joint first authors.R.R. and F.D. contributed equally as joint senior authors.
- Published
- 2016
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