@article{3001547,
    title = "Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma",
    author = "Mansouri, L. and Noerenberg, D. and Young, E. and Mylonas, E. and Abdulla, M. and Frick, M. and Asmar, F. and Ljungström, V. and Schneider, M. and Yoshida, K. and Skaftason, A. and Pandzic, T. and Gonzalez, B. and Tasidou, A. and Waldhueter, N. and Rivas-Delgado, A. and Angelopoulou, M. and Ziepert, M. and Arends, C.M. and Couronné, L. and Lenze, D. and Baldus, C.D. and Bastard, C. and Okosun, J. and Fitzgibbon, J. and Dörken, B. and Drexler, H.G. and Roos-Weil, D. and Schmitt, C.A. and Munch-Petersen, H.D. and Zenz, T. and Hansmann, M.-L. and Strefford, J.C. and Enblad, G. and Bernard, O.A. and Ralfkiaer, E. and Erlanson, M. and Korkolopoulou, P. and Hultdin, M. and Papadaki, T. and Grønbæk, K. and Lopez-Guillermo, A. and Ogawa, S. and Küppers, R. and Stamatopoulos, K. and Stavroyianni, N. and Kanellis, G. and Rosenwald, A. and Campo, E. and Amini, R.-M. and Ott, G. and Vassilakopoulos, T.P. and Hummel, M. and Rosenquist, R. and Damm, F.",
    journal = "Blood advances",
    year = "2016",
    volume = "128",
    number = "23",
    pages = "2666-2670",
    publisher = "American Society of Hematology",
    doi = "10.1182/blood-2016-03-704528",
    keywords = "bleomycin;  cyclophosphamide;  doxorubicin;  immunoglobulin enhancer binding protein;  prednisolone;  prednisone;  rituximab;  vincristine;  vindesine;  I kappa B;  NFKBIE protein, human;  oncoprotein;  tumor marker, acute lymphoblastic leukemia;  adult;  aged;  Article;  B cell lymphoma;  cancer immunotherapy;  cancer patient;  cancer prognosis;  cancer radiotherapy;  cancer survival;  classical Hodgkin lymphoma;  clinical outcome;  comparative study;  controlled study;  diffuse large B cell lymphoma;  female;  follicular lymphoma;  follow up;  gene;  gene deletion;  gene expression profiling;  gene frequency;  genetic association;  Hodgkin disease;  human;  major clinical study;  male;  mantle cell lymphoma;  mediastinum cancer;  mutational analysis;  NFKBIE gene;  nucleotide sequence;  primary central nervous system lymphoma;  primary tumor;  priority journal;  regulatory mechanism;  splenic marginal zone lymphoma;  T cell leukemia;  treatment response;  whole exome sequencing;  adolescent;  B cell lymphoma;  clinical trial;  disease free survival;  genetics;  mediastinum tumor;  middle aged;  mortality;  multicenter study;  survival rate, Adolescent;  Adult;  Aged;  Biomarkers, Tumor;  Disease-Free Survival;  Female;  Gene Deletion;  Humans;  I-kappa B Proteins;  Lymphoma, B-Cell;  Male;  Mediastinal Neoplasms;  Middle Aged;  Proto-Oncogene Proteins;  Survival Rate",
    abstract = "We recently reported a truncating deletion in the NFKBIE gene, which encodes IκB, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n 5 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 central nervous system lymphoma (3% to 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 5 .022) and displayed inferior outcome compared with wild-Type patients (5-year survival, 59% vs 78%; P 5 .034); however, they appeared to benefit from radiotherapy (P 5 .022) and rituximab-containing regimens (P 5 .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P 5 .003) and when restricting the analysis to immunochemotherapy-Treated patients (P 5 .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. © 2016 by The American Society of Hematology."
}