{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001005436"],"host":["EGA"],"description":["EGA study EGAS00001005436"],"dataset_title":["G-SAM: Transcriptional Evolution of Glioblastomas Treated With Standard of Care"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["<h4>Purpose</h4>Precision medicine trials in glioblastoma (GBM) are often conducted at tumor recurrence. However, second surgeries for recurrent GBM are not routinely performed, and therefore, molecular data for trial inclusion are predominantly derived from the primary sample. This study aims to establish whether molecular targets change during tumor progression and, if so, whether this affects precision medicine trial design.<h4>Materials and methods</h4>We collected 186 pairs of primary-recurrent GBM samples from patients receiving chemoradiotherapy with temozolomide and sequenced approximately 300 cancer genes. <i>MGMT</i>, <i>TERT</i>, and <i>EGFRvIII</i> status was individually determined.<h4>Results</h4>The molecular profile of our cohort was identical to that of other GBM cohorts (<i>IDH</i> wild-type [WT], 95%; <i>EGFR</i> amplified, approximately 50%), indicating that patients amenable to second surgery do not represent a specific molecular subtype. Molecular events in <i>IDH</i> WT GBMs were stable in approximately 80% of events, but changes in mutation status were observed for all examined genes (range, approximately 90% and 60% for <i>TERT</i> and <i>EGFR</i> mutations, respectively), and such changes strongly affected targeted trial size and design. A similar pattern of GBM driver instability was observed within <i>MGMT</i> promoter-methylated tumors. <i>MGMT</i> promoter methylation status remained prognostic at tumor recurrence. The observation that hypermutation at GBM recurrence was rare (8%) and not correlated with outcome was relevant for immunotherapy-based treatments.<h4>Conclusion</h4>This large cohort of matched primary and recurrent <i>IDH</i> WT tumors establishes the frequency of GBM driver instability after chemoradiotherapy with temozolomide. This allows per gene or pathway calculation of trial size at tumor recurrence, using molecular data of the primary tumor only. We also identify genes for which repeat surgery is necessary because of low mutation retention rate."],"pubmed_title":["Molecular Evolution of <i>IDH</i> Wild-Type Glioblastomas Treated With Standard of Care Affects Survival and Design of Precision Medicine Trials: A Report From the EORTC 1542 Study."],"pubmed_authors":["Draaisma Kaspar K, Chatzipli Aikaterini A, Taphoorn Martin M, Kerkhof Melissa M, Weyerbrock Astrid A, Sanson Marc M, Hoeben Ann A, Lukacova Slávka S, Lombardi Giuseppe G, Leenstra Sieger S, Hanse Monique M, Fleischeuer Ruth R, Watts Colin C, McAbee Joseph J, Angelopoulos Nicos N, Gorlia Thierry T, Golfinopoulos Vassilis V, Kros Johan M JM, Verhaak Roel G W RGW, Bours Vincent V, van den Bent Martin J MJ, McDermott Ultan U, Robe Pierre A PA, French Pim J PJ"],"description_synonyms":["glioblastoma multiforme, grade IV adult astrocytic tumour, Glioblastoma, grade IV adult astrocytic tumor, Analyses, Determination, spongioblastoma multiforme, Sequence Determination, Glioblastomas, GBM, study., RNA-seq, Giant Cell, Grade IV, Giant Cell Glioblastoma, Astrocytomas, Sequence Determinations, sample population, Sequencing, Astrocytoma, DNA Sequence Determination, Determinations, DNA Sequence Analysis, adult glioblastoma multiforme, Glioblastoma Multiforme, DNA Sequence Analyses, Grade IV Astrocytomas, grade IV adult Astrocytic tumor, primary glioblastoma multiforme, sample, DNA Sequencing, DNA Sequence Determinations, Whole Transcriptome Shotgun Sequencing, glioblastoma, Grade IV Astrocytoma, DNA Sequence, DNA, Analysis, Giant Cell Glioblastomas, Sequence Analyses, DNA sequencing"],"pubmed_title_synonyms":["isocitrate dehydrogenase, Idh-NADP, Care Standards, Predictive Medicine, IDH, Idh, Individualized Medicine, ICD-M, Affects, FBgn0038922, A4, IDP, l(3)L3852, mNADP-IDH, Progress Reports, Giant Cell, Grade IV, Personalized, Astrocytomas, TYPE, IDCD, LGMD2C, DAGA4, survival, Investigative, Investigative Report, Personalized Medicine, idh, Summary Report, Research Reports, HEL-S-26, Mood, Precision, MAM, Giant Cell Glioblastomas, Standards of Care, HEL-216, SCG3, Summary Reports, PICD, IDHM, Cytosolic NADP-isocitrate dehydrogenase, Molecular Evolution, Glioblastoma, Genetic, Individualized, DMDA1, death rate, CT22171, Progress Report, CG7176, Moods, Field, Glioblastomas, study., D2HGA2, Theranostic, Evolution, Giant Cell Glioblastoma, NADP(+)-specific ICDH, Oxalosuccinate decarboxylase, DmelCG7176, Astrocytoma, 1.1.1.42, Progress, Glioblastoma Multiforme, Report, IDH-NADP, DMDA, IDH2, Field Reports, Grade IV Astrocytomas, P-Health, Reports, DmelCG6439, time of survival, IDPC, Theranostics, SCARMD2, Medicine, P Health, Grade IV Astrocytoma, Predictive, Investigative Reports, Summary, IDPM, Genetic Evolution, Care Standard, Field Report"],"name_synonyms":["l(3)Ca, Care Standards, titin, l(3)62Ca, d-titin, (3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, 0020/01, [1-(adenin-9-yl)-1, Giant Cell, Grade IV, SLS, Sls, Astrocytomas, SAMe, kettin, AdoMet, DmelCG1915, Titin, Giant Cell Glioblastomas, Standards of Care, anon-CREST, Ket, SAM, D-titin, l(3)j1D7, Glioblastoma, Acylcarnitine, Care Standard., S-adenosylmethionine, Glioblastomas, S-(5'-deoxyadenosin-5'-yl)-L-methionine, D-Titin, CG18857, Giant Cell Glioblastoma, ket, 5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium, sam, Astrocytoma, sal, l(3)dre8, Glioblastoma Multiforme, CG1915, CT41299, Grade IV Astrocytomas, S-Adenosylmethionine, KZ, l(3)S002001, l(3)rL182, CG18242, Grade IV Astrocytoma, MCP, inner salt, CG18245"],"pubmed_abstract_synonyms":["DER/faint little ball, isocitrate dehydrogenase, Materials, O6-alkylguanine-DNA alkyltransferase, Concurrent Chemoradiotherapies, Repeat, retention., Individualized Medicine, FBgn0038922, Elp-B1, der, Elp-1, Mbp1, A4, Errb1, mNADP-IDH, Tumor, Astrocytomas, Repeat Surgery, hTRT, Neoplasm Genes, DNA-6-O-methylguanine:protein-L-cysteine S-methyltransferase activity, PIG61, Mutations, Techniques, primary tumour, Method, epidermal growth factor-activated receptor activity, Joint, AI552599, hEST2, DKCB4, DNA-6-O-methylguanine:[protein]-L-cysteine S-methyltransferase activity, Methazolastone, 2, 3, Relapses, d-egf-r, Chemoradiotherapies, preoperative procedures, myd, PICD, Cytosolic NADP-isocitrate dehydrogenase, me75, CCRG81045, DKCA2, Moods, Recurrences, Mbp-1, D2HGA2, procedures, M&B39831, Giant Cell Glioblastoma, D17Mit170, Concomitant, flb, T1, Astrocytoma, NADP(+)-specific ICDH, Concomitant Chemoradiotherapies, Methodological Studies, grade IV adult Astrocytic tumor, IDPC, sample, Medicine, Therapies, 9030024J15Rik, s, D-EGFR, Malignancies, IDPM, NISBD2, TR, Tumors, DER1, 1-d)-1, Surgical Revision, Therapy, Relapse, Elp, TMZA-HE, Wa5, l(2)09261, gyltl1b-b, IDH, Idh, DEgfr, frequency, IDP, l(3)L3852, Giant Cell, Procedure, Tl3, Tl2, M&B-39831, CG10079, IDCD, 5-tetrazin-4(3H)-one, DNA-6-O-methylguanine - [protein]-L-cysteine S-methyltransferase activity, Temodal, torpedo/egfr, Benign, wa2, Recrudescence, Personalized Medicine, primary glioblastoma multiforme, 6-O-methylguanine-DNA methyltransferase activity, idh, MDDGA6, mKIAA0609, Genetic Materials, Revision Surgeries, General, KIAA0609, Genetic Material, 6-O-methylguanine-DNA methyltransferase, DNA-6-O-methylguanine - protein-L-cysteine S-methyltransferase activity, egfr, fg, Concomitant Radiochemotherapy, Glioblastoma, HD-33, El, Immunotherapies, gyltl1b, O-6-methylguanine-DNA-alkyltransferase activity, TCS1, CT22171, spongioblastoma multiforme, DER/EGFR, EGFR, EGfr, EgfR, dEgfr, mdc1d, NSC 362856, expanded, GBM, Benign Neoplasms, DER flb, NSC-362856, INSDC_feature:gene, Methodological, Cancer Gene, Torpedo/Egfr, Temodar, Methodological Study, surveillance, Treatments, morbidity, Oxalosuccinate decarboxylase, Malignant Neoplasms, Degfr, 1.1.1.42, MDC1D, Surgical, MGMT, Agat, DMDA, Grade IV Astrocytomas, enr, Patient, enlarged, Material, primary tumor, DmelCG6439, DEGFR, Theranostics, AGT, l(2)57DEFa, l(2)05351, CCRG-81045, dEGFR, Cistron, DmHD-33, other neoplasm, invasive procedures, big, Concurrent, D-Egf, Procedures, Concomitant Chemoradiotherapy, Chemoradiotherapy, C-erb, Neoplasms, Benign Neoplasm, mor1, Temozolomide Hexyl Ester, Gene, Surgery, TMZ-Bioshuttle, Grade IV, mENA, EK2-6, Malignant, TYPE, froggy, Gyltl1a, DAGA4, large, CCRG 81045, c-erbB, EGFr, Egfr, Studies, torpedo/Egfr, EGF receptor activity, glioblastoma, Mood, TOP, Precision, Egf-r, Low, TP2, TMZ Bioshuttle, MAM, Giant Cell Glioblastomas, HEL-216, SCG3, Technique, study, IDHM, EGF-R, Individualized, grade IV adult astrocytic tumor, Genetic, Malignancy, occurrence, Recrudescences, Synchronous Chemoradiotherapies, MDDGB6, prevalence, top, Torpedo/DER, LARGE, Radiochemotherapy, EGFRvIII, DmelCG7176, top/flb, Concurrent Radiochemotherapies, Neoplasias, Study, BPFD#36, Glioblastoma Multiforme, Cancer Genes, IDH-NADP, IDH2, CMM9, l(2)57EFa, Clients, great, l(2)57Ea, Grade IV Astrocytoma, operative procedures, Predictive, Methylations, incidence, Cancer, AI267024, Elp-B1RB1, grade IV adult astrocytic tumour, data, Idh-NADP, Malignant Neoplasm, cou, Predictive Medicine, TGF-alpha receptor activity, ERBB, dEGFR1, Affects, ICD-M, Synchronous, Concurrent Radiochemotherapy, intraoperative procedures, TRT, M&B 39831, Personalized, methylated-DNA-protein-cysteine S-methyltransferase activity, Cistrons, Client, LGMD2C, 8-Carbamoyl-3-methylimidazo(5, adult glioblastoma multiforme, Lr, epidermal growth factor receptor activity, DmelCG10079, peroperative procedures, EST2, HEL-S-26, Neoplasm, Revision, Revision Surgery, techniques, methylation, DER/top, outbreaks, INSDC_feature:regulatory, Radiochemotherapies, Joint Revision, glioblastoma multiforme, O-6-methylguanine-DNA-alkyltransferase, Genes, DMDA1, top/DER, CG7176, primary neoplasia, storage, operative therapy, Concomitant Radiochemotherapies, Synchronous Chemoradiotherapy, Glioblastomas, operations, Theranostic, ERBB1, Cancers, wa-2, NSC362856, sample population, endemics, Neoplasm Gene, 2.1.1.63, Egf, EFG-R, P-Health, PFBMFT1, Therapeutic, Errp, Erbb, SCARMD2, Der, DER, perioperative procedures, Bra, Concurrent Chemoradiotherapy, P Health, Treatment, epidemics, transforming growth factor-alpha receptor activity, sequestering, Neoplasia, DER/torpedo, HER1, methodology"],"additional_accession":[]},"is_claimable":false,"name":"G-SAM: Transcriptional Evolution of Glioblastomas Treated With Standard of Care","description":"Collection of mostly matching primary and recurrent glioblastoma RNA-seq sample pairs, also matching with an earlier DNA sequencing study","dates":{"updated":"2023-01-13 11:10:20"},"accession":"EGAS00001005436","cross_references":{"TAXONOMY":["9606"],"pubmed":["31743054"],"EGA":["EGAD00001007860","EGAC00001001818"]}}