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Novel Intergenically-spliced Chimera, NFATC3-PLA2G15, is Associated with Aggressive T-ALL Biology and Outcome
Bond et al
Contents:
Supplementary Methods
Supplementary Tables S1-S4
Supplementary Figures S1-S5
Supplementary References
Supplementary Methods:
Extra RNA-sequencing information:
Selection of fusion transcripts required a total of 3 reads spanning two distinct gene transcripts (including at least 1 paired-end read and 1 split read). These filters are recommended by the manufacturer (Life Technologies), and we have previously used these criteria to sensitively and specifically identify leukemia-associated fusion transcripts ADDIN EN.CITE Bond474717Bond, J.Bergon, A.Durand, A.Tigaud, I.Thomas, X.Asnafi, V.Spicuglia, S.Macintyre, E.Universite Sorbonne Paris Cite, Faculty of Medicine Descartes, INSERM U1151, Laboratory of Onco-Hematology, Assistance Publique-Hopitaux de Paris, Hopital Necker-Enfants Malades, Paris, France.
Transcriptomic and Genomic Marseille-Luminy, Infrastructures en Biologie Sante et Agronomie Platform, Marseille, France Technological Advances for Genomics and Clinics, INSERM U1090, Aix-Marseille University Unite Mixtes de Recherche-S 1090, Marseille, France.
Universite Sorbonne Paris Cite, Faculty of Medicine Descartes, INSERM U1151, Laboratory of Onco-Hematology, Assistance Publique-Hopitaux de Paris, Hopital Necker-Enfants Malades, Paris, France.
Cytogenetic and Molecular Biology Laboratory, Centre Hospitalier Lyon Sud, Pierre-Benite, France.
Department of Hematology, Hopital Edouard Herriot, Lyon, France.
Universite Sorbonne Paris Cite, Faculty of Medicine Descartes, INSERM U1151, Laboratory of Onco-Hematology, Assistance Publique-Hopitaux de Paris, Hopital Necker-Enfants Malades, Paris, France.
Technological Advances for Genomics and Clinics, INSERM U1090, Aix-Marseille University Unite Mixtes de Recherche-S 1090, Marseille, France.
Universite Sorbonne Paris Cite, Faculty of Medicine Descartes, Institut Necker-Enfants Malades, INSERM U1151, Laboratory of Onco-Hematology, Assistance Publique-Hopitaux de Paris, Hopital Necker-Enfants Malades, Paris, France.Cryptic XPO1-MLLT10 translocation is associated with HOXA locus deregulation in T-ALLBloodBloodBloodBloodBloodBlood3023-512419AdultGene Expression Regulation, LeukemicHomeodomain Proteins/*geneticsHumansKaryopherins/*geneticsLeukemia-Lymphoma, Adult T-Cell/*geneticsMaleReceptors, Cytoplasmic and Nuclear/*geneticsTranscription Factors/*genetics*Translocation, GeneticNov 061528-0020 (Electronic)
0006-4971 (Linking)25377562http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=25377562 engBond424217Bond, J.Marchand, T.Touzart, A.Cieslak, A.Trinquand, A.Sutton, L.Radford-Weiss, I.Lhermitte, L.Spicuglia, S.Dombret, H.Macintyre, E.Ifrah, N.Hamel, J. F.Asnafi, V.Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
Department of Hematology, University Hospital and INSERM UMR 917, Rennes 1 University, Rennes
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
Department of Hematology, Centre Hospitalier Argenteuil
Universite Paris 5 Descartes, Department of Cytogenetics, Assistance PubliqueHopitaux de Paris, Hopital Necker-Enfants Malades, Paris
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
Technological Advances for Genomics and Clinics (TAGC), INSERM U1090, Aix-Marseille University UMR-S 1090, Marseille
Universite Paris Diderot, Institut Universitaire d'Hematologie, EA-3518, Assistance Publique-Hopitaux de Paris, University Hospital Saint-Louis, Paris
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, Paris
PRES LUNAM, CHU Angers Service des Maladies du Sang et INSERM U 892, Angers, France
PRES LUNAM, CHU Angers Service des Maladies du Sang et INSERM U 892, Angers, France
Universite Paris Descartes Sorbonne Cite, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Medicale (INSERM) U1151, and Laboratory of OncoHematology, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker EnfantsMalades, ParisAn early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia studyHaematologicaHaematologicaHaematologicaHaematologicaHaematologicaHaematologica732-401016Jun1592-8721 (Electronic)
0390-6078 (Linking)26944475http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=26944475 eng(1, 2).
Fusions that involved genes located within 30 kb of each other with the same transcriptional orientation were defined as candidate ISCs. This distance was chosen as the majority of ISCs that have been previously observed in the literature have been described to involve genes located within this proximity ADDIN EN.CITE Nacu494917Nacu, S.Yuan, W.Kan, Z.Bhatt, D.Rivers, C. S.Stinson, J.Peters, B. A.Modrusan, Z.Jung, K.Seshagiri, S.Wu, T. D.Department of Bioinformatics and Molecular Biology, Genentech, Inc, South San Francisco, California 94080, USA.Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samplesBMC Med GenomicsBMC medical genomicsBMC Med GenomicsBMC medical genomicsBMC Med GenomicsBMC medical genomics114Adenocarcinoma/*genetics/pathologyBase SequenceComparative Genomic Hybridization/methodsDatabases, GeneticExpressed Sequence Tags*Gene FusionHumansMaleProstatic Neoplasms/*genetics/pathologyReference StandardsReverse Transcriptase Polymerase Chain Reaction/methodsSequence Analysis, RNA/*methodsJan 241755-8794 (Electronic)
1755-8794 (Linking)21261984http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21261984 engAkiva2006262617Akiva, P.Toporik, A.Edelheit, S.Peretz, Y.Diber, A.Shemesh, R.Novik, A.Sorek, R.Compugen Ltd., Tel Aviv 69512, Israel.Transcription-mediated gene fusion in the human genomeGenome ResGenome researchGenome ResGenome researchGenome ResGenome research30-6161Evolution, MolecularGene Fusion/*geneticsGenome, Human/*geneticsHumansJurkat CellsK562 CellsRNA Splicing/*geneticsTranscription, Genetic/*genetics2006Jan1088-9051 (Print)
1088-9051 (Linking)16344562http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16344562 engQin353517Qin, F.Song, Z.Babiceanu, M.Song, Y.Facemire, L.Singh, R.Adli, M.Li, H.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America; Pharmacy Department of Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cellsPLoS GenetPLoS geneticsPLoS GenetPLoS geneticsPLoS GenetPLoS geneticse1005001112Base SequenceCell FusionCell Line, TumorExons*Gene Expression ProfilingGene Expression Regulation, Neoplastic*Gene FusionGenome, HumanHumansMaleProstatic Neoplasms/*genetics/pathologyRNA Splicing/geneticsRepressor Proteins/*geneticsSequence Analysis, RNAFeb1553-7404 (Electronic)
1553-7390 (Linking)25658338http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=25658338 eng(3-5).
Supplementary Table S1: Details of sequencing depth.
Patient numberTotal readsMapped readsT-ALL 1122989096111614301T-ALL 26591429458969866T-ALL 39618817286425581T-ALL 48801334479440148T-ALL 58929926479235938T-ALL 66173342055960260T-ALL 76293826656294505T-ALL 87890125870297296T-ALL 99952952688880089T-ALL 107953114670766987T-ALL 119750556483731973T-ALL 124887488642953504
Supplementary Table S2: List of genes used for GSEA shown in Figure 2B. This list is taken from http://www.ncbi.nlm.nih.gov/biosystems/137993
Supplementary Table S4: (Corresponds to Figures 1D, 3C and 3D)
Comparison of NFATC3-PLA2G15 high and low cases treated during the GRAALL-2003 and -2005 studies.
NFATC3-PLA2G15 HighNFATC3-PLA2G15 LowTotalp-valueTotal (%) 30 (24.4%)93 (75.6%)123 (100%)Clinical Subsets AnalyzedMale22 (73.3%)64 (68.8%)86 (69.9%)0.64Median Age (years)30.934.133.10.53W B C ( 1 0 9 / l , m e d i a n ) 3 6 . 0 3 7 . 0 3 7 . 0 0 . 4 6 C N S i n v o l v e m e n t 4 ( 1 3 . 3 % ) 1 1 ( 1 1 . 8 % ) 1 5 ( 1 2 . 2 % ) 0 . 8 3 T - c e l l r e c e p t o r s t a t u s I m m a t u r e ( I M 0 , I M D , I M G # ) 7 ( 2 5 . 9 % ) 2 3 ( 2 7 . 4 % ) 3 0 ( 2 7 . 0 % ) 0 . 8 8 l i n e a g e 2 0 ( 7 4 . 1 % ) 5 1 ( 6 0 . 7 % ) 7 1 ( 6 4 . 0 % ) 0 . 2 1 l i n e a g e 0 (0%)10 (11.9%)10 (9.0%)0.06ETP immunophenotype#2 (7.4%)21 (24.7%)23 (18.7%)0.05OncogeneticsNOTCH1/ FBXW7 mutated17 (56.7%)66 (71.0%)83 (67.5%)0.15RAS/ PTEN mutated11 (39.3%)10 (10.9%)21(17.5%)< 0.001Risk Classifier# 16 (55.2%)33 (35.5%)49 (40.2%)0.06Treatment ResponseCorticosensitivity19 (63.3%)44 (47.3%)63 (51.2%)0.13Complete Remission27 (90.0%)87 (93.5%)114 (92.7%)0.52MRD positivity4 (25.0%)17 (30.4%)21 (29.2%)0.68
# T-cell receptor gene status (n = 111), ETP immunophenotype (n = 112) and Risk classifier based on genotype for NOTCH1, FBXW7, PTEN, NRAS and KRAS (n = 122) were determined as previously described ADDIN EN.CITE Asnafi2003444417Asnafi, V.Beldjord, K.Boulanger, E.Comba, B.Le Tutour, P.Estienne, M. H.Davi, F.Landman-Parker, J.Quartier, P.Buzyn, A.Delabesse, E.Valensi, F.Macintyre, E.Department of Biological and Clinical Hematology, Centre Hospitalier-Universitaire/Assistance Publique-Hopitaux de Paris (CHU/AP-HP) Necker-Enfants Malades and Universite Paris V, France.Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitmentBloodBloodBloodBloodBloodBlood2693-7031017AdolescentAdultAgedAntigens, CD/analysisCell LineageChildGenotypeHomeodomain Proteins/*geneticsHumansImmunophenotypingLeukemia-Lymphoma, Adult T-Cell/classification/immunology/*pathologyMaleMembrane Glycoproteins/*geneticsMiddle AgedRNA, Messenger/analysisReceptors, Antigen, T-Cell/*classificationReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocytes/*cytology2003Apr 010006-4971 (Print)
0006-4971 (Linking)12446444http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12446444 engCoustan-Smith2009454517Coustan-Smith, E.Mullighan, C. G.Onciu, M.Behm, F. G.Raimondi, S. C.Pei, D.Cheng, C.Su, X.Rubnitz, J. E.Basso, G.Biondi, A.Pui, C. H.Downing, J. R.Campana, D.Department of Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemiaLancet OncolThe LancetLancet OncolThe LancetLancet OncolThe Lancet147-56102AdolescentChildChild, PreschoolDrug Resistance, Neoplasm/*geneticsFemaleFlow Cytometry*Gene Expression ProfilingHumansImmunophenotypingInfantKaplan-Meier EstimateMalePolymorphism, Single NucleotidePrecursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*pathology/therapyRisk Factors2009Feb1474-5488 (Electronic)
1470-2045 (Linking)19147408http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19147408 engTrinquand434317Trinquand, A.Tanguy-Schmidt, A.Ben Abdelali, R.Lambert, J.Beldjord, K.Lengline, E.De Gunzburg, N.Payet-Bornet, D.Lhermitte, L.Mossafa, H.Lheritier, V.Bond, J.Huguet, F.Buzyn, A.Leguay, T.Cahn, J. Y.Thomas, X.Chalandon, Y.Delannoy, A.Bonmati, C.Maury, S.Nadel, B.Macintyre, E.Ifrah, N.Dombret, H.Asnafi, V.Amelie Trinquand, Raouf Ben Abdelali, Etienne Lengline, Noemie De Gunzburg, Ludovic Lhermitte, Jonathan Bond, Agnes Buzyn, Elizabeth Macintyre, and Vahid Asnafi, University Paris Descartes, Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR)-8147, and Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker-Enfants Malades; Jerome Lambert, UMR-S-717, Hopital Saint-Louis, AP-HP; Kheira Beldjord, Etienne Lengline, and Herve Dombret, University Paris 7, Hopital Saint-Louis, AP-HP, and Institut Universitaire d'Hematologie, EA3518, Paris; Aline Tanguy-Schmidt and Norbert Ifrah, Pole de Recherche et d'Enseignement Superieur L'Universite Nantes Angers Le Mans, Centre Hospitalier Universitaire Angers Service des Maladies du Sang et L'Institut National de la Sante et de la Recherche Medicale (INSERM) U892, Angers; Dominique Payet-Bornet and Bertrand Nadel, Center of Immunology of Marseille Luminy, Aix-Marseille University, INSERM U1104 and Centre National de la Recherche Scientifique (CNRS) UMR-7280, Marseille; Hossein Mossafa, Laboratoire Cerba, Cergy-Pontoise; Veronique Lheritier and Xavier Thomas, Centre Hospitalier Lyon Sud, Lyon; Francoise Huguet, Hopital Purpan, Toulouse; Thibaud Leguay, Centre Hospitalier du Haut Leveque, Pessac; Jean-Yves Cahn, UMR-5525 CNRS-Universite Joseph Fourier, Grenoble; Caroline Bonmati, Centre Hospitalier Regional Hopital de Brabois, Vandoeuvre Les Nancy; Sebastien Maury, Hopital Henry Mondor, Creteil, France; Yves Chalandon, University Hospital of Geneva, Geneva, Switzerland; and Andre Delannoy, Hopital de Jolimont, La Louviere, Belgium.Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia studyJ Clin OncolJ Clin Oncol4333-423134AdultCell Cycle Proteins/*genetics*DNA Mutational AnalysisDisease-Free SurvivalF-Box Proteins/*geneticsFemaleGTP Phosphohydrolases/*genetics*Gene DeletionGenetic Predisposition to DiseaseHumansKaplan-Meier EstimateMaleMembrane Proteins/*geneticsMultivariate Analysis*MutationPTEN Phosphohydrolase/*geneticsPhenotypePrecursor T-Cell LymphoblasticLeukemia-Lymphoma/classification/*genetics/mortality/therapyPredictive Value of TestsProportional Hazards ModelsProto-Oncogene Proteins/*geneticsProto-Oncogene Proteins p21(ras)Receptor, Notch1/*geneticsRisk FactorsTime FactorsUbiquitin-Protein Ligases/*geneticsYoung Adultras Proteins/*geneticsDec 011527-7755 (Electronic)
0732-183X (Linking)24166518http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=24166518 eng(6-8).
Corticosensitivity (n = 123) was defined as clearance of peripheral blood circulating blasts (< 1 x 109/L) following steroid prophase; Complete Remission (n = 123) was defined as clearance of bone marrow blasts (<5%) following induction treatment; MRD positivity (n = 72) was defined at a threshold of 10-4, as determined by allele-specific oligonucleotide PCR at the end of induction treatment.
Supplementary Figure S1: Detection of the NFATC3-PLA2G15 ISC by RNA-sequencing of an independent series of primary T-ALL samples.
Diagnostic RNA from an independent series of 12 primary T-ALL samples was subjected to high-throughput sequencing analysis using the Illumina platform. The Sashimi-plot representation displays splicing junctions in 4 samples positive for NFATC3-PLA2G15 chimeric transcripts (black arrows) with the same involved exons as were detected in the initial patient series. Supplementary Figure S2: 5 RACE PCR.
5 RACE (Rapid Amplification of cDNA ends) PCR was performed using either a fusion-specific primer (Primer NFATC3-PLA2G15), which spanned the fusion breakpoint, or a primer that was positioned 5 to the breakpoint (Primer NFATC3), which could theoretically permit amplification of both the fusion and WT transcripts. Primer positions are depicted schematically in the upper panel.
Representative results of 5 RACE PCR using Primer NFATC3-PLA2G15 (two leukemic samples) and Primer NFATC3 (one leukemic sample) are shown in the lower panel. The sizes of the largest amplified PCR products are consistent with initiation of transcription at the transcriptional start site (TSS) of NFATC3.
Supplementary Figure S3: Array competitive genomic hybridization (CGH).
Array CGH was performed using DNA extracted from 115 T-ALL samples. 112 had no evidence of microdeletion of either the NFATC3 or PLA2G15 loci (data not shown). Analysis of copy number state in the remaining 3 samples is shown in this screengrab (Chromosome Analysis Suite software, Affymetrix), in which the positions of the NFATC3 and PLA2G15 genes are indicated. The image has been modified to remove patient identifications. These 3 cases had possible microdeletions (1 copy number) of the 3 portion of the NFATC3 gene. 2 of the 3 also had apparent gains (3 copy numbers) of other segments of NFATC3. Notably, none of these cases had deletion of any portion of PLA2G15. In summary, none of the 115 T-ALL samples tested had evidence of genomic deletion that would result in generation of the detected NFATC3-PLA2G15 chimeric transcript.
Supplementary Figure S4: NFATC3 protein expression in luciferase assays. (Corresponds to Figure 2A)
Expression of NFATC3 proteins for measurement of luciferase activity was verified by Western Blot. Luciferase reporter activity was normalized to NFATC3 protein levels, which were quantified using the BioRad ChemiDocTM XRS+ machine with Image LabTM software relative to ACTIN run on the same blot. A representative experiment and relative quantification is shown. Protein size is indicated.
Supplementary Figure S5: Patient samples used for murine xenografts.
The graph depicts the levels of NFATC3-PLA2G15 in patient samples used for murine xenografts (left panel). Levels across the entire patient cohort, including the cases used for xenografts are shown for comparison (right panel).
Supplementary References:
ADDIN EN.REFLIST 1. Bond J, Bergon A, Durand A, et al. Cryptic XPO1-MLLT10 translocation is associated with HOXA locus deregulation in T-ALL. Blood 2014;124(19):3023-5.
2. Bond J, Marchand T, Touzart A, et al. An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. Haematologica 2016;101(6):732-40.
3. Nacu S, Yuan W, Kan Z, et al. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples. BMC medical genomics 2011;4:11.
4. Akiva P, Toporik A, Edelheit S, et al. Transcription-mediated gene fusion in the human genome. Genome research 2006;16(1):30-6.
5. Qin F, Song Z, Babiceanu M, et al. Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells. PLoS genetics 2015;11(2):e1005001.
6. Asnafi V, Beldjord K, Boulanger E, et al. Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood 2003;101(7):2693-703.
7. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. The Lancet 2009;10(2):147-56.
8. Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol 2013;31(34):4333-42.
No ISCs were detected in samples T-ALL 4 and T-ALL 12. Chromosomal coordinates correspond to version hg19 of the human genome. RPKM = Reads per kb per million mapped reads. PE = Paired-End.
Supplementary Table S3: List of candidate intergenically spliced chimeras
NFATC3
PLA2G15
T-ALL 15
T-ALL 14
T-ALL 16
T-ALL 13
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