{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Ute Fischer"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000509"],"host":["EGA"],"description":["EGA DAC EGAC00001000509"],"repository":["EGA"],"email":["ute.fischer@med.uni-duesseldorf.de"],"pubmed_abstract":["Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are not commonly used in clinical practice for treatment of B-cell lymphomas, although a subset of patients with refractory or relapsed B-cell lymphoma achieved partial or complete remissions. Therefore, the purpose of this study was to identify molecular features that predict the response of B-cell lymphomas to SAHA treatment. We designed an integrative approach combining drug efficacy testing with exome and captured target analysis (DETECT). In this study, we tested SAHA sensitivity in 26 B-cell lymphoma cell lines and determined SAHA-interacting proteins in SAHA resistant and sensitive cell lines employing a SAHA capture compound (CC) and mass spectrometry (CCMS). In addition, we performed exome mutation analysis. Candidate validation was done by expression analysis and knock-out experiments. An integrated network analysis revealed that the Src tyrosine kinase Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR) is associated with SAHA resistance. FGR was specifically captured by the SAHA-CC in resistant cells. In line with this observation, we found that FGR expression was significantly higher in SAHA resistant cell lines. As functional proof, CRISPR/Cas9 mediated FGR knock-out in resistant cells increased SAHA sensitivity. In silico analysis of B-cell lymphoma samples (n = 1200) showed a wide range of FGR expression indicating that FGR expression might help to stratify patients, which clinically benefit from SAHA therapy. In conclusion, our comprehensive analysis of SAHA-interacting proteins highlights FGR as a factor involved in SAHA resistance in B-cell lymphoma."],"pubmed_title":["A novel approach to detect resistance mechanisms reveals FGR as a factor mediating HDAC inhibitor SAHA resistance in B-cell lymphoma."],"pubmed_authors":["Joosten Maria M, Ginzel Sebastian S, Blex Christian C, Schmidt Dmitri D, Gombert Michael M, Chen Cai C, Linka René Martin RM, Gräbner Olivia O, Hain Anika A, Hirsch Burkhard B, Sommerfeld Anke A, Seegebarth Anke A, Gruber Uschi U, Maneck Corinna C, Zhang Langhui L, Stenin Katharina K, Dieks Henrik H, Sefkow Michael M, Münk Carsten C, Baldus Claudia D CD, Thiele Ralf R, Borkhardt Arndt A, Hummel Michael M, Köster Hubert H, Fischer Ute U, Dreger Mathias M, Seitz Volkhard V"],"pubmed_title_synonyms":["less than 500 grams, B-Cell Lymphoma, foetal Growth retardation, 249 grams, HDAC Inhibitor, non-Hodgkin's B-cell lymphoma, FET GROWTH RET 750-999G, foetal SGA, B-cell NHL, B-cell non-Hodgkin lymphoma, B-Cell, Poor fetal growth state, Histone, Histone Deacetylase Inhibitor, lymphomas non-Hodgkin's B-cell, FET GROWTH RETARD <500G, unspecified [weight], p58-Fgr, B Cell, unspecified, Fetal Growth Retardation, 750-1, 999 grams, FET GROWTH RETARD WTNOS, resistance, FGR, FET GRWTH RET 1250-1499G, 1, 2, foetal small for gestational Age, NOS, Inhibitors, intrauterine Growth restriction, IUGR, fetal SGA, Lymphomas, HDAC, FET GRWTH RET 1000-1249G, Intrauterine growth retardation, B-cell, SRC2, FET GROWTH RET 500-749G, fetal small for gestational Age, FET GRWTH RET 1500-1749G, Fetal growth retardation NOS (disorder), Fetal growth retardation (disorder), FET GROWTH RET 2500+G, Microsomic baby, Histone Deacetylase, non-Hodgkin's lymphoma B-cell, fetal growth restriction, B-cell lymphocytic neoplasm, IUGR - Intrauterine growth retardation, 500-1, foetal growth retardation, fetal growth retardation, 500+ grams, Deacetylase Inhibitor, B Cell Lymphoma, Fetal growth retardation NOS, Poor fetal growth, FGR - Fetal growth retardation, p55-Fgr, intrauterine Growth retardation, c-src2, fetus small for gestational Age, lymphoma, 250-1, 500-749 grams, foetus small for gestational Age, 750-999 grams, B-Cell Lymphomas, Lymphoma, 000-1, c-fgr, 000-2, B-cell lymphoma., p55c-fgr, Microsomia, B-cell non Hodgkin's lymphoma, Deacetylase Inhibitors, p58c-fgr, Foetal growth retardation, FET GRWTH RET 2000-2499G, Fetal growth retardation, \"B-cell neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:413616009], 749 grams, 499 grams, HDAC Inhibitors, FET GRWTH RET 1750-1999G, Inhibitor, B-cell non-Hodgkin's lymphoma, fetal Growth retardation"],"pubmed_abstract_synonyms":["src-1, para Tyrosine, B Cells, insensitive, Product, determination, Bursa-Dependent Lymphocytes, FET GROWTH RET 750-999G, B cell, pp60v-src, Germinoblastoma, CCMS, HDRP, Poor fetal growth state, lymphomas non-Hodgkin's B-cell, DmelCG7471, Dm SRC41, Mutations, B Cell, Histone H2b, Malignant Lymphomas, Histone H2a, unspecified, FET GROWTH RETARD WTNOS, responsivity, Pharmaceutical Product, DHDAC1, Line, DHDAC3, FET GRWTH RET 1250-1499G, 1, DHDAC4, 2, intrauterine Growth restriction, Kinase, dRPD3, Analysis, fetal SGA, dRpd3, Lymphomas, Dmel_CG7873, hdac1, hdac3, hdac4, HDAC, Reticulolymphosarcoma, Hydroxamic, Mass Spectrum Analysis, treatment, FET GRWTH RET 1000-1249G, increased, FET GRWTH RET 1500-1749G, Analyses, Fetal growth retardation (disorder), 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, src64B, CG7524, xsrc, fetal growth restriction, 500-1, Y, Hdac 3, fetal growth retardation, Fetal growth retardation NOS, Poor fetal growth, FGR - Fetal growth retardation, allergic reaction, Malignant Lymphoma, Sarcoma, ASV, CCM syndrome, c-src2, fetus small for gestational Age, B lymphocyte, Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, 250-1, 500-749 grams, medicine, Pharmaceutical, Tyr, disease management, Histone H5, Therapies, p55c-fgr, Histone H4, Histone H7, \"B-cell neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:413616009], ATP Phosphotransferases, FET GRWTH RET 1750-1999G, B-cell non-Hodgkin's lymphoma, Histone H1, ATP, Histone H3, Tk5, less than 500 grams, Therapy, B-Cell Lymphoma, foetal Growth retardation, wide/broad, non-Hodgkin's B-cell lymphoma, B Lymphocytes, CG7471, csrc, foetal SGA, DmHD-29, 2-Amino-3-(p-hydroxyphenyl)propionic acid, B-cell non-Hodgkin lymphoma, DRpd3, para-Tyrosine, Spectrum Analysis, rpd[3], Tyrosine, Spectroscopy, Su(phl)1, DmelCG44128, unspecified [weight], Reticulolymphosarcomas, Fetal Growth Retardation, dmHDA405, dmHDA402, HD-29, dmHDA401, NOS, GC1770, Pharmaceutic, Germinoblastic, SK2-4, Hydroxamic Acid, Su(var)3-26, HD7, SRC 64B, Su(D-raf)1, HD9, Lines, Acid, Transphosphorylases, drpd3, SRC2, FET GROWTH RET 500-749G, fetal small for gestational Age, resistant, Src1, SRC1, dSrc, FET GROWTH RET 2500+G, MRE5, L-isomer, Exomes, Spectrometry, c-SRC, B-cell lymphocytic neoplasm, IUGR - Intrauterine growth retardation, Germinoblastomas, foetal growth retardation, E(var)3-64BC, Treatments, Dromel_CG2128_FBtr0078767_hdac3_mORF, L isomer, DmelCG7524, wide, lymphoma, Patient, Specificity and Sensitivity, B-Lymphocyte, Lymphoma, c-fgr, Microsomia, c-src, Foetal growth retardation, Acids, L-Tyrosine, FET GRWTH RET 2000-2499G, D-Src64B, 749 grams, src1, 499 grams, HDAC-1, src2, Proto-oncogene c-Fgr, accessory, Dsrc, DmelCG1770, whole exome, l(3)64Cc, 249 grams, RPD3, dHDAC-1, Dsrc41, cerebro-costo-mandibular syndrome, D-src, B-cell NHL, CG14471, C-src1, B-Cell, Gene, Su(Raf)1, Dm SRC1, Spectrum Analyses, broad, Malignant, Germinoblastic Sarcoma, supernumerary, DSrc, FET GROWTH RETARD <500G, HD7b, DmHD-358, 750-1, sensitive, src64, 999 grams, resistance, dsrc, HDAC7B, Gene Products, Mass, IUGR, rpd3, p60-Src, sensitivity, Phosphotransferase, Histone H3.3, Mass Spectroscopy, MITR, Drugs, Sarcomas, study, reactivity, Intrauterine growth retardation, network topology analysis, Src64, B-cell, dHDAC4, Src42a, dHDAC3, Fetal growth retardation NOS (disorder), Dsrc64, p58c-Fgr, dHDAC1, Transphosphorylase, 500+ grams, l(3)04556, p55-Fgr, drugs, 2.7.10.2, intrauterine Growth retardation, L Tyrosine, Clients, DSrc64, 000-1, 000-2, Sensitivity, p58c-fgr, dtk-5, SRC 42A, HD-358, Fetal growth retardation, Preparation, pp60c-src, Tyrosin, B-lymphoma cell, SRC42A, DSrc64B, CG2128, HDAC9B, Pharmaceuticals, DSRC64, fetal Growth retardation, Products, Src42, Src41, CG44128, src42a, drug, Proteins, Cell Lines, dtk5, Hdac1, Histone, HDAC9FL, Client, Cell, Phosphotransferases, p58-Fgr, MS, rib Gap defects with micrognathia, tirosina, Su(var)326, chemical analysis, Protein, src42A, FGR, src64b, foetal small for gestational Age, Germinoblastic Sarcomas, Su(var)328, CG7873, CG1770, Dsrc42A, Mass Spectrum Analyses, DSrc42A, Mass Spectrum, HDAC3, l(2)k10108, HDAC1, Src, DmelCG2128, Pharmaceutic Preparations, Kinases, increased number, HDAC7, Microsomic baby, non-Hodgkin's lymphoma B-cell, Specificity, AW259666, Dmel_CG14471, Bursa-Equivalent Lymphocyte, Histone H1(s), B Cell Lymphoma, Rpd3/HDAC, Drug, Protein Gene Products, Gene Proteins, present in greater numbers in organism, Preparations, src, Therapeutic, src42, foetus small for gestational Age, 750-999 grams, B-Cell Lymphomas, Su1, B-cell lymphoma., B-cell non Hodgkin's lymphoma, DmHDAC3, HDAC4a, Treatment, DmHDAC1, assay, response, B-lymphocyte, Pharmaceutical Products, Dtk5, CEREBROCOSTOMANDIBULAR syndrome, Dsrc64B, Pharmaceutical Preparation, B-cell lymphoma"],"additional_accession":[]},"is_claimable":false,"name":"SAHA-ZIM Data Access Committee","description":"Data Access Committee EGAC00001000509","dates":{"output":"2025-1-9"},"accession":"EGAC00001000509","cross_references":{"TAXONOMY":["9606"],"pubmed":["27324824"],"EGA":["EGAS00001001463","EGAD00001002262"]}}