{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000536"],"host":["EGA"],"description":["EGA study EGAS00001000536"],"dataset_title":["T-ALL transcriptome sequence study"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["RNA-seq is a promising technology to re-sequence protein coding genes for the identification of single nucleotide variants (SNV), while simultaneously obtaining information on structural variations and gene expression perturbations. We asked whether RNA-seq is suitable for the detection of driver mutations in T-cell acute lymphoblastic leukemia (T-ALL). These leukemias are caused by a combination of gene fusions, over-expression of transcription factors and cooperative point mutations in oncogenes and tumor suppressor genes. We analyzed 31 T-ALL patient samples and 18 T-ALL cell lines by high-coverage paired-end RNA-seq. First, we optimized the detection of SNVs in RNA-seq data by comparing the results with exome re-sequencing data. We identified known driver genes with recurrent protein altering variations, as well as several new candidates including H3F3A, PTK2B, and STAT5B. Next, we determined accurate gene expression levels from the RNA-seq data through normalizations and batch effect removal, and used these to classify patients into T-ALL subtypes. Finally, we detected gene fusions, of which several can explain the over-expression of key driver genes such as TLX1, PLAG1, LMO1, or NKX2-1; and others result in novel fusion transcripts encoding activated kinases (SSBP2-FER and TPM3-JAK2) or involving MLLT10. In conclusion, we present novel analysis pipelines for variant calling, variant filtering, and expression normalization on RNA-seq data, and successfully applied these for the detection of translocations, point mutations, INDELs, exon-skipping events, and expression perturbations in T-ALL."],"pubmed_title":["Comprehensive analysis of transcriptome variation uncovers known and novel driver events in T-cell acute lymphoblastic leukemia."],"pubmed_authors":["Atak Zeynep Kalender ZK, Gianfelici Valentina V, Hulselmans Gert G, De Keersmaecker Kim K, Devasia Arun George AG, Geerdens Ellen E, Mentens Nicole N, Chiaretti Sabina S, Durinck Kaat K, Uyttebroeck Anne A, Vandenberghe Peter P, Wlodarska Iwona I, Cloos Jacqueline J, Foà Robin R, Speleman Frank F, Cools Jan J, Aerts Stein S"],"pubmed_title_synonyms":["T-cell acute lymphocytic leukaemia, acute T cell lymphoblastic leukemia, T-cell acute lymphocytic leukemia, T-cell leukemia, Transcriptome, precursor T-lymphoblastic leukemia (T-cell ALL), T-ALL., determination, Transcriptome Profile, T-cell ALL, Profile, T-cell acute lymphoblastic leukemia, Expression Profiles, Gene Expression Profile, Gene, T acute lymphoblastic leukemia, acute T-cell lymphocytic leukemia, Profiles, T-cell type acute leukemia, Signatures, Gene Expression, precursor T-lymphoblastic lymphoma/leukemia, Expression Signature, Gene Expression Profiles, Expression Signatures, acute T-cell leukemia, chemical analysis, Gene Expression Signatures, T-cell lymphoblastic leukemia/lymphoma, Transcriptomes, T Acute Lymphoblastic Leukemia, acute T cell leukaemia, acute T cell leukemia, Precursor T Lymphoblastic Leukemia, assay, Gene Expression Signature, Signature, acute T-cell lymphoblastic leukemia, precursor T-lymphoblastic leukemia, Expression Profile, acute T cell lymphocytic leukemia, Transcriptome Profiles"],"name_synonyms":["T-cell acute lymphocytic leukaemia, acute T cell lymphoblastic leukemia, T-cell acute lymphocytic leukemia, T-cell leukemia, Materials, precursor T-lymphoblastic leukemia (T-cell ALL), Genetic, T-cell ALL, T-cell acute lymphoblastic leukemia, Point Mutations, Gene, INSDC_feature:gene, T acute lymphoblastic leukemia, acute T-cell lymphocytic leukemia, RNA-seq., T-cell type acute leukemia, Cistrons, Mutations, precursor T-lymphoblastic lymphoma/leukemia, Material, Point, acute T-cell leukemia, T-cell lymphoblastic leukemia/lymphoma, T Acute Lymphoblastic Leukemia, Genetic Materials, Whole Transcriptome Shotgun Sequencing, Cistron, acute T cell leukaemia, acute T cell leukemia, Precursor T Lymphoblastic Leukemia, acute T-cell lymphoblastic leukemia, precursor T-lymphoblastic leukemia, Mutation, Genetic Material, acute T cell lymphocytic leukemia, T-ALL"],"pubmed_abstract_synonyms":["AI504024, acute T cell lymphoblastic leukemia, T-cell leukemia, Dfps, NK-2, Materials, tumor suppressor, FADK2, hTM30nm, TPMsk3, HOX11, determination, RAFTK, Hox-11, CFTD, precursor T-cell acute lymphoblastic leukemia/lymphoma, OK|SW-cl.5, Mini Exon, acute T-cell lymphocytic leukemia, Rbtn1, CG8874, protein, JTK10, Precursor T Cell Lymphoblastic Lymphoma, Raftk, Acute., Mutations, cell cycle regulator, BCH, Acute T-Cell Leukemia, CAKB, dfps, T-Lymphocytic Leukemia, Line, TCL3, HD-179, 26Fe, Transforming, 2310079I02Rik, protein aggregate, Precursor T Cell Lymphoblastic Leukemia, NKX2.1, Hox11, T-ALL, T-Lymphocytic Leukemias, T-cell acute lymphocytic leukemia, Flk, precursor T-lymphoblastic leukemia (T-cell ALL), Gene Expressions, T-cell ALL, Leucocythemias, OK/SW-cl.5, TEBP, H3.3A, Transforming Genes, RBTN1, CAKbeta, Rbtn-1, acute T-cell leukemia, Tpm-5, Nkx2.1, FERONIA, Bx, Nucleotide, precursor T-cell acute lymphoblastic leukemia, mKIAA4140, SSDP2, dfer, Acute T-Cell Leukemias, CG11849, Arts, RNA-seq, JAK2, results, dfps85D, PSA, soss-b2, dFer, THCYT3, DmelCG8874, batch, JAK-2, T-Cell, TYK3, DFER, DFer, TM30, Genetic Materials, acute T cell leukaemia, acute T cell leukemia, ZNF912, RHOM1, precursor T-lymphoblastic leukemia, END, Genetic Material, BHC, nucleotides, Lines, Lymphoblastic Leukemia, T-cell acute lymphocytic leukaemia, Leucocythemia, Industrial, T Cell Leukemia, PTK, Acute T-Lymphocytic Leukemias, Factors, Industrial Arts, FPS, Iron, Dm FPS, lmo1, Pe1Fe6, Exomes, Pe1Fe3, precursor T-cell acute lymphocytic leukemia/lymphoma, INSDC_feature:gene, lmo3, Acute T-Lymphocytic Leukemia, STAT5, TM3, TM5, tlx1-a, Fe, precursor T-cell acute lymphocytic leukemia, Pe1Fe13, Eisen, Pe1Fe10, Oncogene, fps, Patient, A830008M03Rik, Material, stat5, XHox11, DmHD-179, hscp30, Dfer, Cistron, T Cell, AV026640, H3F3, iron, Fert2, whole exome, Lymphocytic Leukemia, TTF1, E430023O05Rik, Gene, Janus kinase 2, protein-containing complex, AF10, Transcription Factor, h3f3a, T-Cell Leukemias, precursor T-lymphoblastic lymphoma/leukemia, Tpm5, T-Cell Acute Lymphocytic Leukemia, TTF-1, Mini-Exon, Gene Products, T Acute Lymphoblastic Leukemia, leukaemia NOS, AW558684, Whole Transcriptome Shotgun Sequencing, C81284, fps85D, PYK2, Precursor T-Cell Lymphoblastic Leukemia, Leucocythaemia, Pyk2, Trop-5, acute T-cell lymphoblastic leukemia, Af10, Ttf-1, h3.3a, Fert, Lymphocytic, h3.3b, Transcription, hierro, Leukemia, Genetic, Transforming Gene, 9330163K02Rik, Precursor T-Cell Lymphoblastic Lymphoma, CADTK, Expressions, gamma-TM, NEM1, FerT, FAK2, SGPA, HEL-S-82p, Acute T-Lymphocytic, Clients, Ttg1, TTG1, T-cell lymphoblastic leukemia/lymphoma, Dan, T|EBP, Fer, FER, Expression, CAPM1, Acute T-Cell, TM30nm, HHT1, 1500004K09Rik, dfps 85D, hTMnm, C330004K01Rik, D630001B22Rik, Edg, protein complex, TRK, Flk_retired, T-cell acute lymphoblastic leukemia, Proteins, Cell Lines, fer, Point Mutations, T acute lymphoblastic leukemia, Factor, T-cell type acute leukemia, Cistrons, XHox11L2, Titf1, Client, Leukemias, Cell, T-Cell Leukemia, DmelCG11849, RGD1563655, NKX2A, Fd17, PKB, native protein, TITF1, Tm5NM, Protein, Hspc116, chemical analysis, sequence, Mutation, acute T cell lymphocytic leukemia, B130021D15Rik, Acute T Cell, Leucocythaemias, ferrum, Genes, TM-5, AV082135, exonic region, SOSS-B2, Mini-Exons, Lymphoblastic, Exon, patient, HEL-189, PPP1R74, hox11, primary structure of sequence macromolecule, T Lymphocytic Leukemia, TMnm, Protein Gene Products, h3.3, Gene Proteins, Acute, Point, AU067692, Precursor T Cell Lymphoblastic Leukemia Lymphoma, HSPC116, Precursor T Lymphoblastic Leukemia, assay, ORW1"],"description_synonyms":["acute T cell lymphoblastic leukemia, T-cell leukemia, Materials, tumor suppressor, Lymphocytic Leukemia, precursor T-cell acute lymphoblastic leukemia/lymphoma, Gene, acute T-cell lymphocytic leukemia, RNA-seq., Transcription Factor, Precursor T Cell Lymphoblastic Lymphoma, T-Cell Leukemias, Mutations, precursor T-lymphoblastic lymphoma/leukemia, cell cycle regulator, T-Cell Acute Lymphocytic Leukemia, Acute T-Cell Leukemia, T-Lymphocytic Leukemia, T Acute Lymphoblastic Leukemia, leukaemia NOS, Line, Whole Transcriptome Shotgun Sequencing, Transforming, Precursor T-Cell Lymphoblastic Leukemia, Leucocythaemia, acute T-cell lymphoblastic leukemia, Precursor T Cell Lymphoblastic Leukemia, T-ALL, T-Lymphocytic Leukemias, Lymphocytic, T-cell acute lymphocytic leukemia, Transcription, Leukemia, precursor T-lymphoblastic leukemia (T-cell ALL), Genetic, Gene Expressions, Transforming Gene, T-cell ALL, Precursor T-Cell Lymphoblastic Lymphoma, Leucocythemias, Expressions, Transforming Genes, Acute T-Lymphocytic, Clients, acute T-cell leukemia, T-cell lymphoblastic leukemia/lymphoma, Expression, Nucleotide, Acute T-Cell, precursor T-cell acute lymphoblastic leukemia, protein-coding, HHT1, Edg, Acute T-Cell Leukemias, Arts, T-cell acute lymphoblastic leukemia, Cell Lines, Point Mutations, RNA-seq, T acute lymphoblastic leukemia, Factor, T-cell type acute leukemia, Cistrons, Client, Leukemias, Cell, T-Cell Leukemia, T-Cell, sequence, Genetic Materials, acute T cell leukaemia, acute T cell leukemia, precursor T-lymphoblastic leukemia, END, Mutation, Genetic Material, acute T cell lymphocytic leukemia, nucleotides, Acute T Cell, Leucocythaemias, Lines, Lymphoblastic Leukemia, T-cell acute lymphocytic leukaemia, Leucocythemia, Industrial, T Cell Leukemia, Genes, Acute T-Lymphocytic Leukemias, Factors, Industrial Arts, Lymphoblastic, precursor T-cell acute lymphocytic leukemia/lymphoma, INSDC_feature:gene, patient, Acute T-Lymphocytic Leukemia, primary structure of sequence macromolecule, T Lymphocytic Leukemia, precursor T-cell acute lymphocytic leukemia, Acute, Oncogene, Patient, Material, Point, Precursor T Cell Lymphoblastic Leukemia Lymphoma, Cistron, Precursor T Lymphoblastic Leukemia, T Cell, ORW1"],"additional_accession":[]},"is_claimable":false,"name":"Identification of point mutations, expression perturbations, and gene fusions in T-cell acute lymphoblastic leukemia by RNA-seq","description":"RNA-seq is a promising technology to re-sequence protein-coding genes for the identification of single nucleotide variants, while simultaneously obtaining information on structural variations and gene expression perturbations. T-cell acute lymphoblastic leukemia (T-ALL) is caused by a combination of gene fusions leading to the over-expression of transcription factors reinforced by point mutations in oncogenes and tumor suppressor genes. We asked whether RNA-seq is suitable for the detection of driver mutations in these leukemias. We analyzed 31 T-ALL patient samples and 18 T-ALL cell lines by high-coverage paired-end RNA-seq.","dates":{"updated":"2024-10-22 13:09:58"},"accession":"EGAS00001000536","cross_references":{"TAXONOMY":["9606"],"pubmed":["24367274"],"EGA":["EGAD00001000849","EGAC00001002939"]}}