EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD00001000702190EGA dataset EGAD00001000702EGAMantle cell lymphoma (MCL) is an aggressive malignancy that is characterized by poor prognosis. Large-scale pharmacological profiling across more than 100 hematological cell line models identified a subset of MCL cell lines that are highly sensitive to the B cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin. Sensitive MCL models exhibited chronic activation of the BCR-driven classical nuclear factor-κB (NF-κB) pathway, whereas insensitive cell lines displayed activation of the alternative NF-κB pathway. Transcriptome sequencing revealed genetic lesions in alternative NF-κB pathway signaling components in ibrutinib-insensitive cell lines, and sequencing of 165 samples from patients with MCL identified recurrent mutations in TRAF2 or BIRC3 in 15% of these individuals. Although they are associated with insensitivity to ibrutinib, lesions in the alternative NF-κB pathway conferred dependence on the protein kinase NIK (also called mitogen-activated protein 3 kinase 14 or MAP3K14) both in vitro and in vivo. Thus, NIK is a new therapeutic target for MCL treatment, particularly for lymphomas that are refractory to BCR pathway inhibitors. Our findings reveal a pattern of mutually exclusive activation of the BCR-NF-κB or NIK-NF-κB pathways in MCL and provide critical insights into patient stratification strategies for NF-κB pathway-targeted agents.Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma.Rahal Rami R, Frick Mareike M, Romero Rodrigo R, Romero Rodrigo R, Korn Joshua M JM, Kridel Robert R, Chan Fong Chun FC, Meissner Barbara B, Bhang Hyo-eun HE, Ruddy Dave D, Kauffmann Audrey A, Farsidjani Ali A, Derti Adnan A, Rakiec Daniel D, Naylor Tara T, Pfister Estelle E, Kovats Steve S, Kim Sunkyu S, Dietze Kerstin K, Dörken Bernd B, Steidl Christian C, Tzankov Alexandar A, Hummel Michael M, Monahan John J, Morrissey Michael P MP, Fritsch Christine C, Sellers William R WR, Cooke Vesselina G VG, Gascoyne Randy D RD, Lenz Georg G, Stegmeier Frank FVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPphapii, IPP2A2, BamF, bim, biml, BamC, bam, igaad, StF-IT-1, ham, BOD, PHAPII, group, fs(3)neo61, 5730420M11Rik, CG10422, I-2PP2A, Dm I-2, I2PP2A, bim-beta7, bod, DmelCG10422, bimel, SET, HLA-DR-associated protein II, ensemble, DI-2, TAF-I, HCAP, bim-beta6, I-2Dm, ipp2a2, study., 2pp2a, CG4299, alpha, CDLS3, BMH, CG10574, DmelCG4299, I-2PP1, IGAAD, set, dSET/TAF-Ibeta, 2610030F17Rik, TAF-IBETA, 2PP2A, BIM, DmelCG10574, taf-ibeta, Bam-C, BAM, Bam, dSET, dSet, SMC3L1, TAF-Ibeta, CSPG6, AA407739, i2pp2aMantle-Zone Lymphoma, mantle cell, treatment, Therapy, Lymphocytic, Centrocytic Small Cell, Mantle-Cell Lymphoma, Mantle-Zone, Small-Cell Lymphomas, Centrocytic Small-Cell, Centrocytic, Intermediate, Small-Cell Lymphoma, Treatments, Diffuse, genomic profiling, Mantle Cell Lymphoma., Small-Cell, Mantle Cell, lymphoma, Lymphocytic Lymphoma, Centrocytic Small-Cell Lymphomas, Therapeutic, Poorly-Differentiated, Mantle-Zone Lymphomas, Lymphoma, disease management, Therapies, Mantle Zone Lymphoma, Centrocytic Small-Cell Lymphoma, Treatment, Mantle-Cell Lymphomas, Diffuse Lymphocytic Lymphoma, Poorly Differentiated, Intermediate Differentiated, Lymphomas, Mantle-CellMantle-Zone Lymphoma, mantle cell, Cognitive Function, scale tissue, Centrocytic Small Cell, B Cells, PCI-32765, acetylglucosaminyltransferase-like protein, Bursa-Dependent Lymphocytes, B cell, Mbp1, dTraf2, HSP 17, Gene Expression Profile, l(3)6286, Profiles, AIP1, Germinoblastoma, Tumor, mcIAP1, Mutations, Malignant Lymphomas, Techniques, Line, BCR, symptoms, CG40494, Kinase, myd, Lymphomas, BCR1, Reticulolymphosarcoma, AU045934, treatment, HAIP1, LRCC, Prognoses, cIAP2, like-acetylglucosaminyltransferase, cIAP1, cIAP-2, cIAP-1, Small-Cell Lymphomas, plant peltate hair, Mbp-1, Signatures, genetic, allergic reaction, AI853148, TRAP3, CG10961, Malignant Lymphoma, Sarcoma, Cognitions, B lymphocyte, Expression Signature, Functions, CIAP2, disease management, Transcriptomes, Therapies, Malignancies, ATP Phosphotransferases, MGC - 45012, ATP, single organism signaling, Tumors, Therapy, screening, DMSN, gyltl1b-b, B Lymphocytes, AW107670, Expression Profiles, familial, Centrocytic, Test, MIAP2, MIAP1, CG16973, Insight, D22S662, Gene Expression, 6286, AW146227, Reticulolymphosarcomas, Benign, MDDGA6, mKIAA0609, Expression Signatures, JNKKKK, HLRCC, Germinoblastic, dtraf2, KIAA0609, Expression Profile, AI325259, acetylglucosaminyltransferase-like 1A, activation, AI561783, Lines, Transcriptome Profiles, ITRAF, fg, Transphosphorylases, Factors, gyltl1b, In Vitro, Prognostic, Tests, mdc1d, signs, Benign Neoplasms, IAP2, Germinoblastomas, LARGE_HUMAN, IAP1, CG17960, Treatments, Malignant Neoplasms, dTRAF2, MDC1D, SNF1-RELATED PROTEIN KINASE 2-2, dTRAF6, lymphoma, Centrocytic Small-Cell Lymphomas, enr, antagonists and inhibitors, Patient, B-Lymphocyte, SNF1-related protein kinase 2.2, Lymphoma, Centrocytic Small-Cell Lymphoma, Mantle-Cell Lymphomas, PCI 32765, inherited genetic, Poorly Differentiated, Mantle Cell Lymphoma, Protein Kinase, Prognostic Factor, Dmel_CG00000, TRAF, LMP1 Associated Protein 1, TRAP, In Vitro as Topic, Testings, Transcriptome Profile, HS, Neoplasms, peltate hair, 5133400C09Rik, Benign Neoplasm, Gene, I-TRAF, l(3)j1E2, MEKKK4, Prognostic Factors, HSNIK, Malignant, Germinoblastic Sarcoma, LARGE1, froggy, Gyltl1a, In Vitro Testing, CML, RNF48, CG17617, RNF49, Client., sensitive, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo(3, HGK, Phytomitogen, LMP1-Associated Protein 1, rhoGAP1A, Intermediate Differentiated, sensitivity, Phosphotransferase, Technique, In Vitro Tests, DmelCG40494, FTDCR1B, Lymphocytic, Sarcomas, MESR5, B-cell, In, Malignancy, MDDGB6, D22S11, Profile, inhibiteur, PHL, LARGE, Small-Cell Lymphoma, EG:23E12.5, Transphosphorylase, HIAP1, dependence, HIAP2, FLH21957, ATP-protein phosphotransferase, EG:23E12.2, l(3)03349, Diffuse, Cognitive Functions, Neoplasias, BPFD#36, Mantle Cell, DTRAF2, MGC:45012, API2, SNRK2-2, inhibidor, 4-d)pyrimidin-1-yl)piperidin-1- yl)prop-2-en-1-one, Api2, Api1, MSN, Msn, Poorly-Differentiated, Clients, Mantle Zone Lymphoma, 9430080K19Rik, Chronic, Diffuse Lymphocytic Lymphoma, MCL, DmelCG10961, MCUL1, Heat shock 17 kDa protein, constitutitional genetic, AEB071, Cancer, ALL, inhibitors, Imbruvica, HEL-S-31, msm, Transcriptome, findings, Mantle-Cell Lymphoma, Malignant Neoplasm, Birc3, Birc2, Cell Lines, Intermediate, inhibitor, PCI32765, Factor, Protein 3, Traf2, Client, Cell, Phosphotransferases, Testing, Insights, DmelCG16973, SRK2D, In Vitro Test, MT, c-IAP2, TRAF2, CG40453, Gene Expression Signatures, Protein, aly, Neoplasm, In Vitro Testings, MIHB, MIHC, Germinoblastic Sarcomas, Gene Expression Signature, TRAF6, scales, Vitro Testing, Mitogen, HspB3, Mantle-Cell, antagonists, CLECSF8, l(3)06946, SPK-2-2, scale, Mantle-Zone, Kinases, MALT2, Centrocytic Small-Cell, Function, TNF Receptor Associated Factor 2, Bursa-Equivalent Lymphocyte, patient, Cancers, Cognitive, AW046177, Phytomitogens, AU043147, Small-Cell, traf6, Lymphocytic Lymphoma, like-glycosyltransferase, signalling process, Therapeutic, Mantle-Zone Lymphomas, Gene Expression Profiles, In Vitro Technique, Nik, NIK, Treatment, mKIAA3017, Signature, B-lymphocyte, hereditary, PROTEIN KINASE, Neoplasia, glycosyltransferase-like protein LARGE1falseena-DATASET-BCCA-06-12-2013-17:57:13:627-21 - samplesComplete set of bam files associated with study EGAS000010006222022-11-22 12:10:04EGAD00001000702960624362935EGAC00000000011EGAS00001000622