TY - JOUR
TI - Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
AU - Mansouri, L.
AU - Noerenberg, D.
AU - Young, E.
AU - Mylonas, E.
AU - Abdulla, M.
AU - Frick, M.
AU - Asmar, F.
AU - Ljungström, V.
AU - Schneider, M.
AU - Yoshida, K.
AU - Skaftason, A.
AU - Pandzic, T.
AU - Gonzalez, B.
AU - Tasidou, A.
AU - Waldhueter, N.
AU - Rivas-Delgado, A.
AU - Angelopoulou, M.
AU - Ziepert, M.
AU - Arends, C.M.
AU - Couronné, L.
AU - Lenze, D.
AU - Baldus, C.D.
AU - Bastard, C.
AU - Okosun, J.
AU - Fitzgibbon, J.
AU - Dörken, B.
AU - Drexler, H.G.
AU - Roos-Weil, D.
AU - Schmitt, C.A.
AU - Munch-Petersen, H.D.
AU - Zenz, T.
AU - Hansmann, M.-L.
AU - Strefford, J.C.
AU - Enblad, G.
AU - Bernard, O.A.
AU - Ralfkiaer, E.
AU - Erlanson, M.
AU - Korkolopoulou, P.
AU - Hultdin, M.
AU - Papadaki, T.
AU - Grønbæk, K.
AU - Lopez-Guillermo, A.
AU - Ogawa, S.
AU - Küppers, R.
AU - Stamatopoulos, K.
AU - Stavroyianni, N.
AU - Kanellis, G.
AU - Rosenwald, A.
AU - Campo, E.
AU - Amini, R.-M.
AU - Ott, G.
AU - Vassilakopoulos, T.P.
AU - Hummel, M.
AU - Rosenquist, R.
AU - Damm, F.
JO - Blood advances
PY - 2016
VL - 128
TODO - 23
SP - 2666-2670
PB - American Society of Hematology
SN - null
TODO - 10.1182/blood-2016-03-704528
TODO - 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
TODO - 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.
ER -