{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["Illumina HiSeq 2000;"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00001002055"],"sample_count":["242"],"description":["EGA dataset EGAD00001002055"],"repository":["EGA"],"title":["H005 WES CLL"],"pubmed_abstract":["As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non-BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care."],"pubmed_title":["Drug-perturbation-based stratification of blood cancer."],"pubmed_authors":["Dietrich Sascha S, Oleś Małgorzata M, Lu Junyan J, Sellner Leopold L, Anders Simon S, Velten Britta B, Wu Bian B, Hüllein Jennifer J, da Silva Liberio Michelle M, Walther Tatjana T, Wagner Lena L, Rabe Sophie S, Ghidelli-Disse Sonja S, Bantscheff Marcus M, Oleś Andrzej K AK, Słabicki Mikołaj M, Mock Andreas A, Oakes Christopher C CC, Wang Shihui S, Oppermann Sina S, Lukas Marina M, Kim Vladislav V, Sill Martin M, Benner Axel A, Jauch Anna A, Sutton Lesley Ann LA, Young Emma E, Rosenquist Richard R, Liu Xiyang X, Jethwa Alexander A, Lee Kwang Seok KS, Lewis Joe J, Putzker Kerstin K, Lutz Christoph C, Rossi Davide D, Mokhir Andriy A, Oellerich Thomas T, Zirlik Katja K, Herling Marco M, Nguyen-Khac Florence F, Plass Christoph C, Andersson Emma E, Mustjoki Satu S, von Kalle Christof C, Ho Anthony D AD, Hensel Manfred M, Dürig Jan J, Ringshausen Ingo I, Zapatka Marc M, Huber Wolfgang W, Zenz Thorsten T"],"description_synonyms":["Data Set., Controlling, preventive therapy, Complete Exome Sequencings, Malignant Neoplasm, Complete Exome, Neoplasms, Exome, Benign Neoplasm, Germinoblastoma, Tumor, Malignant, Germinoblastic Sarcoma, prevention, Malignant Lymphomas, Exome Sequencing, Reticulolymphosarcomas, Benign, Neoplasm, Germinoblastic Sarcomas, Whole Transcriptome, Transcriptome Sequencing, Germinoblastic, prevention and control, Lymphomas, Reticulolymphosarcoma, Sarcomas, WES, Complete Transcriptome, Complete, Complete Transcriptome Sequencing, Exome Sequencings, reference sample, Malignancy, prophylaxis, Complete Exome Sequencing, Whole Transcriptome Sequencing, Benign Neoplasms, Cancers, MLYM, Germinoblastomas, Sequencing, Malignant Neoplasms, Neoplasias, preventive measures, Malignant Lymphoma, Sarcoma, Whole Exome, lymphoma, control, Whole, Lymphoma, Whole Exome Sequencing, Malignancies, other neoplasm, Transcriptome Sequencings, Neoplasia, Controlled, lymphoid cancer, Cancer, Tumors"],"name_synonyms":["Vasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASP"],"pubmed_title_synonyms":["Hematological Malignancies, hematopoietic neoplasm, Products, \"blood cancer\" EXACT [CSP2005:2004-0139], \"Hematological tumors\" EXACT [NCI2004_11_17:C27134], Product, \"hematopoietic tumors\" EXACT [NCI2004_11_17:C27134], \"hematopoietic cancer\" EXACT [], Blood, Neoplasms, drug, Hematologic, Hematological Neoplasm, \"Hematologic neoplasm (disorder)\" EXACT [SNOMEDCT_2005_07_31:129154003], Hematopoietic Neoplasm, Hematopoietic Malignancy, Blood Cancers, Pharmaceutical Product, Neoplasm, Hematopoietic Malignancies, hematopoietic cancer, Pharmaceutic, malignant haematopoietic neoplasm (morphologic abnormality), hematopoietic tumors, Drugs, \"Hematologic malignancy (disorder)\" EXACT [SNOMEDCT_2005_07_31:127221002], Hematopoietic, malignant hematopoietic neoplasm (morphologic abnormality), hematopoietic and lymphoid system tumor, \"hematopoietic and lymphoid system tumor\" EXACT [], Pharmaceutic Preparations, haematopoietic cancer, Malignancy, Hematological tumors, Blood Cancer, Hematological Malignancy., malignant haematopoietic neoplasm, Hematologic Malignancies, Hematopoietic Neoplasms, hematologic malignancy, blood cancer, malignant hematopoietic neoplasm, Drug, Preparations, Hematological Neoplasms, drugs, Hematologic Malignancy, medicine, Pharmaceutical, hematologic cancer, Hematological, Hematologic Neoplasm, Malignancies, Hematologic malignancy, Preparation, \"Hematologic malignancy\" EXACT [SNOMEDCT_2005_07_31:269475001], \"hematopoietic neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:414388001], Pharmaceutical Products, Hematologic neoplasm, \"malignant hematopoietic neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:414644002], Pharmaceutical Preparation, Pharmaceuticals, Cancer"],"pubmed_abstract_synonyms":["Kinase Kinases, B Cells, Biological Markers, Viral Marker, 2610315D21Rik, DSORT, Materials, dsor1, MAP-ERK Kinase, Surrogate Endpoints, Product, Partial Trisomies, determination, Laboratory, Bursa-Dependent Lymphocytes, FKBP12-rapamycin complex-associated protein, Globulin, Chromosomal Triplications, B cell, Immune Globulin, Biochemical, Gene Expression Profile, D-MEK/Dsor, Endpoint, MEK1/2, Profiles, DNA Methylations, Tumor, l(2)k03905, Serum, PRKMK7, DmTOR, Mutations, Readability, Laboratory Markers, %, diseases, Biological, responsivity, Pharmaceutical Product, BCR, Su(Raf)34B, diseases and disorders, CG40494, Kinase, RAFT1, Mammalian target of rapamycin, chronic lymphatic, BCR1, human disease, DNA methylation maintenance, Gene Expressions, B-cell chronic lymphocytic leukemia, Genomes, MAPK-ERK Kinases, DNA methylation, DNA Methylomes, DSor1, DSOR1, Signatures, adult chronic leukaemia, dtor, allergic reaction, Map Kinase, AI853148, Map Kinase Kinase, ch, Immune, Markers, B lymphocyte, medicine, Expression Signature, malignant neoplasm, Pharmaceutical, Viral Markers, Transcriptomes, adult chronic leukemia, Homo sapiens disease, Malignancies, chronic lymphatic leukaemia, dSor1, ATP Phosphotransferases, Partial Trisomy, dTOR, dTor, ATP, FK506-binding protein 12-rapamycin complex-associated protein 1, single organism signaling, Tumors, Mechanistic target of rapamycin, Viral, Data Set, SAPKK4, Surrogate Endpoint, sor/MEK1, B Lymphocytes, D-sor-1, Methylomes, Chromosomal Triplication, Expression Profiles, DSor, Partial, Biochemical Markers, Biologic Marker, lymphoplasmacytic leukemia, DRODSOR1, Sensory, Gene Expression, D22S662, Benign, Marker, MAPK, Expression Signatures, Diseases, MAP Kinase Kinases, Genetic Materials, Pharmaceutic, chronic lymphatic leukemia, DMEK-1, lymphocytic, Expression Profile, Methylome, Mitogen Activated Protein Kinase Kinase, RAPT1, dSor, Genetic Material, AI561783, Transcriptome Profiles, EK1-1, Transphosphorylases, MAP ERK Kinase, End Points, Processing, Rapamycin and FKBP12 target 1, Benign Neoplasms, INSDC_feature:gene, whole genome, Immunologic, Laboratory Marker, CG17960, Malignant Neoplasms, dMEK, Phenotypes, disease, immunoglobulin, chromosomal triplication, Specificity and Sensitivity, MAPK-ERK, B-Lymphocyte, Material, Biochemical Marker, 5092, Dsor, chronic lymphocytic leukaemia, Cistron, Globulins, DNA, other neoplasm, MAPK Kinase, Methylation, MAPK Kinases, DNA Methylome, Malignant Neoplasms., Dmel_CG00000, Trisomy, CLL, Cll, other disease, MEKs, MAPKK7, Immunoglobulin, Transcriptome Profile, Clinical Markers, Clinical Marker, Neoplasms, CG5092, MAPK-ERK Kinase, 5133400C09Rik, Benign Neoplasm, chronic LYMPHOCYTIC, Gene, high weight, Malignant, l(2)k17004, B-cell chronic lymphocytic leukaemia, D-mek, Surrogate End Points, cll, CML, antibody, Surrogate Markers, CG17617, sensitive, B-cell chronic lymphoid leukemia, Dmek, heavy, disease or disorder, rhoGAP1A, TOR, JNKK2, sensitivity, Phosphotransferase, CG15793, MAP, Map, DmelCG40494, DmelCG8274, portion of blood, Drugs, reactivity, study, Biomarker, Trisomies, B-cell, MAPK ERK Kinase, Bx34, Genetic, Clinical, MAPKKs, Malignancy, D22S11, Profile, MKK7, Biological Marker, PHL, flat, tor, Tpr, TPR, MEK 7, EG:23E12.5, Transphosphorylase, D-sor, Expressions, EG:23E12.2, Ect5, non-neoplastic, Neoplasias, drugs, Immunologic Markers, Kinase Kinase, Sensitivity, disorder, biological marker, Expression, Preparation, SOR, Sor, Frap1, D-Mek, D-MEK, CT24817, Immunologic Marker, Methylations, CG7937, Biologic, Cancer, Pharmaceuticals, leukemia, ALL, Products, Transcriptome, Encyclopedias, Malignant Neoplasm, whole blood, Mitogen-Activated Protein Kinase Kinase, MAP-ERK, vertebrate blood, drug, Sensory Processing, Serum Markers, disorders, Chronic Lymphocytic Leukemia, lymphoplasmacytic leukaemia, 311, End Point, FRAP1, medical condition, FRAP2, sor, mTOR, Medications, FRAP/TOR, DmelCG5092, Cistrons, Immune Globulins, chronic, Phosphotransferases, MK, Immune Marker, whole transcriptome, MEK/Dsor1, 2.7.11.1, MT, 93Bal, MAPK ERK Kinases, Surrogate End Point, Gene Expression Signatures, chemical analysis, CG40453, Neoplasm, condition, MEK, Mek, MAP Kinase, Gene Expression Signature, D-SOR, D-Sor, Biologic Markers, opsonin activity, DmelCG15793, small lymphocytic lymphoma, primary cancer, Serum Marker, c15, MAPKK, Pharmaceutic Preparations, Epigenomes, Mitogen Activated Protein Kinase Kinases, Kinases, Surrogate, DmelCG7937, Endpoints, Specificity, mek, SAPKK-4, CT24745, Bursa-Equivalent Lymphocyte, Rapamycin target protein 1, AI327068, Cancers, Understanding, FRAP, malignant tumor, Surrogate Marker, Drug, Preparations, Hox11-311, CT16317, signalling process, Gene Expression Profiles, CG8274, MTOR, B cell receptor activity, assay, response, Signature, mKIAA3017, B-lymphocyte, variable, Pharmaceutical Products, Neoplasia, Pharmaceutical Preparation, Immune Markers"],"additional_accession":[]},"is_claimable":false,"name":"ena-DATASET-DKFZ-HIPO-22-04-2016-18:03:44:927-11 - samples","description":"Whole exome sequencing from matched tumor-control samples of 121 primary lymphoma samples. Sequencing was performed on Illumina HiSeq2000. The dataset contains FASTQ files.","dates":{"updated":"2018-05-05 12:51:13"},"accession":"EGAD00001002055","cross_references":{"TAXONOMY":["9606"],"pubmed":["29227286"],"EGA":["EGAC00001000452","EGAS00001001746"]}}