EGAGenomicsIllumina HiSeq 2500;https://ega-archive.org/datasets/EGAD0000100130129EGA dataset EGAD00001001301EGAFollicular lymphoma is an incurable B cell malignancy characterized by the t(14;18) translocation and mutations affecting the epigenome. Although frequent gene mutations in key signaling pathways, including JAK-STAT, NOTCH and NF-κB, have also been defined, the spectrum of these mutations typically overlaps with that in the closely related diffuse large B cell lymphoma (DLBCL). Using a combination of discovery exome and extended targeted sequencing, we identified recurrent somatic mutations in RRAGC uniquely enriched in patients with follicular lymphoma (17%). More than half of the mutations preferentially co-occurred with mutations in ATP6V1B2 and ATP6AP1, which encode components of the vacuolar H(+)-ATP ATPase (V-ATPase) known to be necessary for amino acid-induced activation of mTORC1. The RagC variants increased raptor binding while rendering mTORC1 signaling resistant to amino acid deprivation. The activating nature of the RRAGC mutations, their existence in the dominant clone and their stability during disease progression support their potential as an excellent candidate for therapeutic targeting.Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma.Okosun Jessica J, Wolfson Rachel L RL, Wang Jun J, Araf Shamzah S, Wilkins Lucy L, Castellano Brian M BM, Escudero-Ibarz Leire L, Al Seraihi Ahad Fahad AF, Richter Julia J, Bernhart Stephan H SH, Efeyan Alejo A, Iqbal Sameena S, Matthews Janet J, Clear Andrew A, Guerra-Assunção José Afonso JA, Bödör Csaba C, Quentmeier Hilmar H, Mansbridge Christopher C, Johnson Peter P, Davies Andrew A, Strefford Jonathan C JC, Packham Graham G, Barrans Sharon S, Jack Andrew A, Du Ming-Qing MQ, Calaminici Maria M, Lister T Andrew TA, Auer Rebecca R, Montoto Silvia S, Gribben John G JG, Siebert Reiner R, Chelala Claude C, Zoncu Roberto R, Sabatini David M DM, Fitzgibbon Jude JVasp, VASP, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, Data Set, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, 380., CG15112, ENA/VASPRelapse, WES, Complete Transcriptome, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Complete Exome Sequencings, Complete Exome, Recrudescences, Complete Exome Sequencing, Whole Transcriptome Sequencing, Exome, Recurrences., Client, Sequencing, Exome Sequencing, Whole Exome, relapse, Patient, Recrudescence, Clients, Whole, Whole Exome Sequencing, Whole Transcriptome, Transcriptome Sequencing, Relapses, Transcriptome SequencingsTORC1, Large Follicular Center-Cell, dRagC, Nodular Histiocytic Lymphomas, Small Follicular Center-Cell Lymphoma, Brill-Symmers, Small Cleaved-Cell, Mutations, Nodular Large Follicular Center Cell Lymphoma, Large Lymphoid Lymphoma, Follicular Large-Cell Lymphomas, Small Cleaved Cell Lymphoma, Mixed-Cell Lymphoma, Lymphomas, Follicular, mTORC1 Complex, Mixed Small and Large Cell, Lymphocytic, Histiocytic Lymphoma, Follicular Lymphomas, Follicular., DmelCG8707, Complex, rapamycin and nutrient-sensitive TOR complex, Mixed-Cell Lymphomas, Nodular Large Follicular Center-Cell Lymphoma, Small Follicular Center Cell, Follicular Mixed-Cell Lymphoma, Mixed Cell Lymphoma, Follicular Large-Cell Lymphoma, Small Follicular Center-Cell, Large-Cell, Large Cell Lymphoma, Mixed Small and Large Lymphoid, Large Follicular Center Cell, Histiocytic Lymphomas, Poorly-Differentiated, Nodular, RagC, RAGC, Mixed Lymphocytic-Histiocytic, Giant Follicular, Follicular Lymphoma, ragc, AU041672, Giant Follicular Lymphoma, Disease, TORC 1 complex, Small Lymphoid, dTORC1, Follicular Large Cell, follicular, Large-Cell Lymphomas, Follicular Mixed-Cell, Small and Large Cleaved-Cell, gtr2, YGR163W, Small and Large Cleaved Cell, Mixed Lymphocytic Histiocytic, Rag C, Giant Follicular Lymphomas, Target of Rapamycin Complex 1, Nodular Lymphomas, Mixed Cell, Nodular Histiocytic Lymphoma, Brill Symmers Disease, TOR complex 1, Large Cell, Nodular Lymphoma, Giant, mTORC1, Large-Cell Lymphoma, TIB929, Histiocytic, nutrient sensitive complex, Small Cleaved Cell, dTOR/dRaptor complex, Grade 1, Grade 2, Follicular Mixed-Cell Lymphomas, Grade 3, Brill-Symmers Disease, lymphoma, Lymphocytic Lymphoma, Nodular Histiocytic, TOR Complex 1, Small Follicular Center Cell Lymphoma, GTR2, Lymphoma, Follicular Large-Cell, Gtr2, Follicular Large Cell Lymphoma, Poorly Differentiated, GTPase-interacting protein 2, Large Lymphoid, Small Cleaved-Cell Lymphoma, CG8707, Mixed-Cell, Follicular Mixed Cell LymphomaRap, Dnahc8, Striadyne, B Cells, Materials, dRagC, MENE-R6, acetylglucosaminyltransferase-like protein, Nodular Histiocytic Lymphomas, B cell, Vha68.2, anon-WO02059370.27, Germinoblastoma, Tumor, Mutations, HOP, Hop, CF2, DNA-Dependent ATPase, anon-83Bb, 4, myd, Lymphomas, notch, Follicular, CG17332, vha36, mTORC1 Complex, Progression, Histiocytic Lymphoma, Tum-1, amino acids, like-acetylglucosaminyltransferase, CG8186, Mbp-1, Small Follicular Center Cell, Ax, DmelCG18617, CG17369, DNA Methylomes, vha55, Vha-68-1, high frequency, DNA-Dependent Adenosinetriphosphatases, CrATP, co, Cr(H2O)4 ATP, Xotch, Mixed Lymphocytic-Histiocytic, Giant Follicular, BcDNA.GH03683, dRaptor, BcDNA:GH03683, NECD, single organism signaling, l(1)N, Tumors, ATPsyn-&bgr, Giant Follicular Lymphoma, Small Lymphoid, ATPsyn-b, Chp, B Lymphocytes, Follicular Large Cell, Methylomes, Co, l(3)SzA, DucC, Hst6.7b, VATPS1, DmelCG6213, R74844, Benign, Giant Follicular Lymphomas, mKIAA0609, shd, Magnesium Salt, Atp6s1, TOR complex 1, Nodular Lymphoma, fa, d-jak, activation, fg, DmelCG17332, Acid, DmHD-160, Raptor, nutrient sensitive complex, CG3762, Benign Neoplasms, INSDC_feature:gene, MLYM, Germinoblastomas, vha26, Malignant Neoplasms, Follicular Mixed-Cell Lymphomas, Adenosine, Brill-Symmers Disease, MDC1D, 4320, ATP6B2, lymphoma, C7-1, Nodular Histiocytic, enr, clone 1.12, B-Lymphocyte, Material, HD-160, Lymphoma, Follicular Large-Cell, notch-1, Acids, Prey Birds, Poorly Differentiated, DNA, CG1594, TAN1, GTPase-interacting protein 2, vha16, vha13, DNA Methylome, DmelCG3161, whole exome, Large Follicular Center-Cell, MRE15, BcDNA:LD21735, Magnesium Adenosine Triphosphate, Hop1, Neoplasms, ATP-MgCl2, IB, VhaM9.7-1, LARGE1, Adenylpyrophosphate, P1-Loop, Vma2, DmelCG1088, Large Lymphoid Lymphoma, dRap, CG4320, l(1)Ax, vhaSFD, Sarcomas, DLBCL, Follicular Lymphomas, Birds of Prey, Clinical, MDDGB6, scattered, DmelCG8707, ligand, beta-ATPase, Mixed-Cell Lymphomas, vha68-2, vha68-1, Small Follicular Center-Cell, Neoplasias, Large-Cell, DmelCG17369, ATPase, L4, Clinical Course, ATPasebeta, Poorly-Differentiated, MnATP, ATPase beta, DNA Dependent, ATPB, CT13012, Cancer, 16-178, AU041672, raptor, 16-55, DmelCG4320, Malignant Neoplasm, diffuse, v100, follicular, Large-Cell Lymphomas, vha67-3, vha67-2, anon-EST:Liang-1.12, CG1088, YGR163W, ATP-syn-B, CG12403, DNA Dependent Adenosinetriphosphatases, Small and Large Cleaved Cell, anon-EST:GressD5, Mixed Lymphocytic Histiocytic, MT, CG3161, spl, Neoplasm, Germinoblastic Sarcomas, 1.1, Mixed Cell, vhaM9.7-3, Brill Symmers Disease, nd, vhaM9.7-1, Giant, ATP6IP1, mTORC1, CG11589, HO57, hdhc9, Histiocytic, increased number, Bursa-Equivalent Lymphocyte, Cancers, Small Cleaved Cell, Grade 1, Grade 2, Grade 3, V-ATPase, signalling process, like-glycosyltransferase, TOR Complex 1, Tum, JAK, Jak, l(1)10Be, Small Cleaved-Cell Lymphoma, Neoplasia, V100, CG8707, Calcium Salt, Vhaac39, l(3)05113, xnotch, Adenosine Triphosphate, Bursa-Dependent Lymphocytes, Aminosaeure, Mbp1, VhaAC39, VhaPPA1, CG6213, jak, ATP6V1E1, Small Follicular Center-Cell Lymphoma, Brill-Symmers, Small Cleaved-Cell, Malignant Lymphomas, Follicular Large-Cell Lymphomas, NOTCH, l(1)L4, p150 target of rapamycin (TOR)-scaffold protein, 1208/13, ATP6B1B2, CG7679, VPP3, Mixed-Cell Lymphoma, EP2372, ATPases, ATP6V0D1, Vha68, Mixed Small and Large Cell, Reticulolymphosarcoma, DmelCG1594, Bird of Prey, increased, Chromium Adenosine Triphosphate, mKIAA1303, diffuse large B-cell lymphoma, rapamycin and nutrient-sensitive TOR complex, Vatb, Nodular Large Follicular Center-Cell Lymphoma, Follicular Mixed-Cell Lymphoma, Ac45, Vhac, Large Cell Lymphoma, Malignant Lymphoma, Sarcoma, ATPsyn b, DmelCG3762, notch1-a, Adenosinetriphosphatase, Large Follicular Center Cell, B lymphocyte, Vha1, Disease., Janus kinase activity, VhaG, Exacerbation, VATB, Malignancies, TL, EG:140G11.1, vhaM9.2-1, ATP, VhaD, Chromium Ammonium Salt, VhaE, swb, dTORC1, gyltl1b-b, Aminokarbonsaeure, Disease Exacerbation, XAP-3, SzA, Vha36, BcDNA:LD21248, XAP3, Reticulolymphosarcomas, Atp6b2, 144191_at, Rag C, MDDGA6, vhaAC39-1, Manganese Salt, vha36-1, Nodular Lymphomas, Genetic Materials, DNA-Dependent, VAT-2, DmelCG12403, Germinoblastic, Nodular Histiocytic Lymphoma, anon-WO0118547.296, ATP phosphohydrolase, KIAA0609, Prey Bird, Methylome, Genetic Material, acetylglucosaminyltransferase-like 1A, 16A, Large-Cell Lymphoma, AI194269, ATP6V0C, CG11154, xnotch1, Amino Acid, gyltl1b, mdc1d, Exomes, Triphosphatase, DmelCG11589, Vha16, LARGE_HUMAN, dTOR/dRaptor complex, Adenosinetriphosphatases, DmelCG8186, CaATP, l(2)s4214, Patient, AI790362, msvl, MgATP, Follicular Large Cell Lymphoma, Cistron, ATP6S1, n[fah], Follicular Mixed Cell Lymphoma, accessory, TORC1, vATPase, 4932417H02Rik, Benign Neoplasm, EG:163A10.2, Aminocarbonsaeure, Gene, l(3)87Ca, 1620401A02Rik, CG2934, Malignant, Germinoblastic Sarcoma, supernumerary, froggy, Gyltl1a, Nodular Large Follicular Center Cell Lymphoma, l(2)k07207, vhaPPA1-1, Small Cleaved Cell Lymphoma, ATP-synbeta, Clinical Progression, l(1)3Cb, ATP6V1A, Lymphocytic, B-cell, CG18617, CG1709, Genetic, Malignancy, DmelCG11154, DmelCG3936, Complex, ATP MgCl2, CG7007, LARGE, dNotch, l(2)01510, Mixed Cell Lymphoma, ATP6V1H, l(1)hop, l(3)j2E9, Follicular Large-Cell Lymphoma, ATP6V1D, ATP6V1G, BPFD#36, vha100-2, Chromium Salt, vha100-1, Mixed Small and Large Lymphoid, Histiocytic Lymphomas, Nodular, Clients, RagC, RAGC, raptor/CG4320, Follicular Lymphoma, NICD, vhaAC39, ragc, AI324824, anon-WO0153538.20, DNA Dependent ATPase, anon-WO0153538.21, Disease, TORC 1 complex, Follicular Mixed-Cell, Magnesium Chloride, Small and Large Cleaved-Cell, Adenosine 5'-(tetrahydrogen triphosphate), anon-WO0153538.28, Cistrons, Client, gtr2, Atriphos, ML-1, DmelCG2934, Target of Rapamycin Complex 1, Large Cell, ATP6V1B1, Manganese Adenosine Triphosphate, Adenosine Triphosphatase, frequent, TIB929, Epigenomes, BcDNA:AT14009, Vha, DmelCG1709, Amino, v0a1, vacuolar hydrogen-transporting ATPase, present in greater numbers in organism, Dm JAK, DmelCG7007, Lymphocytic Lymphoma, Small Follicular Center Cell Lymphoma, GTR2, ATPIB, vha, Gtr2, l(1)G18, BcDNA:SD02875, B-lymphocyte, CG3936, Large Lymphoid, Atp6b1b2, Mixed-Cell, vha16-1, glycosyltransferase-like protein LARGE1, lymphoid cancerfalseena-DATASET-BCI-18-03-2015-12:48:54:303-380 - samplesWhole exome sequencing data of 5 patients diagnosed with FL that had undergone several relapse episodes without evidence of transformation2017-07-26 15:39:24EGAD00001001301960626691987EGAC00001000086EGAS00001001190