{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Rogier Versteeg"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000321"],"host":["EGA"],"description":["EGA DAC EGAC00001000321"],"repository":["EGA"],"email":["r.versteeg@amc.uva.nl"],"pubmed_abstract":["The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway. Seven of these events were detected only in the relapse tumor, whereas the others showed clonal enrichment. In neuroblastoma cell lines, we also detected a high frequency of activating mutations in the RAS-MAPK pathway (11/18; 61%), and these lesions predicted sensitivity to MEK inhibition in vitro and in vivo. Our findings provide a rationale for genetic characterization of relapse neuroblastomas and show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease."],"pubmed_title":["Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations."],"pubmed_authors":["Eleveld Thomas F TF, Oldridge Derek A DA, Bernard Virginie V, Koster Jan J, Colmet Daage Léo L, Diskin Sharon J SJ, Schild Linda L, Bentahar Nadia Bessoltane NB, Bellini Angela A, Chicard Mathieu M, Lapouble Eve E, Combaret Valérie V, Legoix-Né Patricia P, Michon Jean J, Pugh Trevor J TJ, Hart Lori S LS, Rader JulieAnn J, Attiyeh Edward F EF, Wei Jun S JS, Zhang Shile S, Naranjo Arlene A, Gastier-Foster Julie M JM, Hogarty Michael D MD, Asgharzadeh Shahab S, Smith Malcolm A MA, Guidry Auvil Jaime M JM, Watkins Thomas B K TB, Zwijnenburg Danny A DA, Ebus Marli E ME, van Sluis Peter P, Hakkert Anne A, van Wezel Esther E, van der Schoot C Ellen CE, Westerhout Ellen M EM, Schulte Johannes H JH, Tytgat Godelieve A GA, Dolman M Emmy M ME, Janoueix-Lerosey Isabelle I, Gerhard Daniela S DS, Caron Huib N HN, Delattre Olivier O, Khan Javed J, Versteeg Rogier R, Schleiermacher Gudrun G, Molenaar Jan J JJ, Maris John M JM"],"name_synonyms":["rocher-Sheldon syndrome, Rossi syndrome, amyoplasia congenita., fibrous ankylosis of multiple joints, Otto syndrome, congenital amyoplasia, myodystrophia fetalis deformans, Guérin-Stern syndrome, Guerin-Stern syndrome"],"pubmed_title_synonyms":["glycogen synthase kinase activity, Ras1/RAs85D, RAS, Ras, DmErk, extracellular signal-regulated kinase activity, l(1)G0098, pp44mapk, protein kinase A activity, Mpk2, c-rasHa, p42mapk, E(sev)3C, Ras-1, CG11485, Prp4 protein kinase activity, SR2-1, ras, c-ras2, LeMPK3, ATP-protein transphosphorylase activity, p44mpk, ATP:protein phosphotransferase (non-specific) activity, kinase-related transforming protein, Dp38, mitogen-activated protein kinase activity, Mutations., SAPK2, mpk1, SEM, Sem, D-Ras1, MAP-k, Erk/Map kinase, RTK, pp42, l(1)G0436, DERK-A, Dsor2, ras85B, ras85D, E(sina)7, sem, Rl, neuroblastoma (morphologic abnormality), Raf kinase activity, [M]Neuroblastoma NOS (morphologic abnormality), MP kinase activity, serine kinase activity, high frequency, DERK, D-ras-2, atypical protein kinase C activity, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, dERK, NB - Neuroblastoma, CG1799, ERK-A, p82 kinase activity, Neuroblastoma (Schwannian Stroma-Poor), l(3)s1747, MAP kinase 2 activity, dpERK, dpErk, Ras2, RAS2, Ras1, RAS1, Mapk, Ki-ras, betaIIPKC, Erk1, ERK1, ERK2, mapk1a, DmMAPK, PMK-2, dp-ERK, PMK-1, Sympathicoblastoma, PMK-3, M phase-specific cdc2 kinase activity, Wee-kinase activity, mapk1b, MapK, MAPK, dRas85D, pMAPK, pMapK, NOS, p21[Ras1], dRas1, dRAS1, ras1, serine protein kinase activity, Dras85D, ras2, erk2, mapk, ras-2, BcDNA:RE36103, ERKa, phosphorylase B kinase kinase activity, l(1)G0351, DmERKA, LD02673, rl/MAPK, BcDNA:RE08694, protein glutamyl kinase activity, Neuroblastomas, DmelCG1799, c-Ha-ras, l(2R)EMS45-39, D-ras1, l(1)G0238, D-ras2, Hras-1, DmelCG12559, C-ras1, non-specific serine/threonine protein kinase activity, p38, Dm Ras1, l(2)41Ac, Dras64B, C-ras2, l(3)06677, DpErk, DpERK, l(1)G0002, ErkA, RasI, ERKA, l(1)G0482, hydroxyalkyl-protein kinase activity, CT34260, WEE1Hu, dpERk, c-H-ras, serine-specific protein kinase activity, epsilon PKC, l(1)G0127, SAPK, HIPK2, cytidine 3', Wee 1-like kinase activity, Harvey-ras, pERK, Hras1, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, neuroblastoma, glycogen synthase A kinase activity, RasV12, GroupII, dRas, Central neuroblastoma, Kras2, glycogen synthase kinase 3 activity, CG1167, 12559, H-ras, DRAS1, DRas2, DmelCG9375, IMPDH, LD06825, phosphorylase b kinase kinase activity, EK2-1, Dras2, Dras1, l(1)G0388, D-Ras, Kras-2, serine(threonine) protein kinase activity, IMPdH, ribosomal protein S6 kinase II activity, Ha-ras, l(1)G0380, Erk, ERK, T-antigen kinase activity, Dras, p21B, PRKM1, ras 1, galactosyltransferase-associated kinase activity, PRKM2, protein-serine kinase activity, dras1, Dm-ras-64B, raspberry/impd, xp42, STK32, Ras[V12], l(1)G0391, EK3-4, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, erk, DRas, DRas85D/Ras, Ras 85D, Dmras64B, protein kinase (phosphorylating) activity, protein-cysteine kinase activity, Raf-1, [M]Neuroblastoma NOS, Hpr kinase activity, rll, DmERK-A, STK26, ras-l, p38-2, casein kinase (phosphorylating) activity, myelin basic protein kinase activity, l(1)G0056, ert1, CG9375, prkm2, stress-activated kinase activity, prkm1, CT39192, MAP-2 kinase activity, K-ras, D-ras-1, protein serine kinase activity, protein phosphokinase activity, E(faf), p38delta, DmelCG1167, fs(3)05703, twitchin kinase activity, PKA, PKC, EP(X)1093, stress-activated protein kinase activity, mapk2, AP50 kinase activity, mapk1, S35097, MBP kinase I activity, NB, AI929937, protein kinase p58 activity, Xp42, serine/threonine protein kinase activity, threonine-specific protein kinase activity, RAS85D, Dmras85D, CG12559, frequent, l(1)9Eb, Neuroblastoma, mitogen activated kinase activity, Su(Raf)2B, dpERK1, EY2-2, dsk1, Su(tor)3-2, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, neuroblastoma NOS (morphologic abnormality), D-ERK, (Neuroblastoma NOS) or (sympathicoblastoma), dpMAPK, protein serine-threonine kinase activity, SAP kinase activity, MAP kinase 1 activity, A-kinase activity"],"pubmed_abstract_synonyms":["Kinase Kinases, RAS, Ras, DmErk, extracellular signal-regulated kinase activity, l(1)G0098, pp44mapk, DSORT, Surrogate Endpoints, Laboratory, acetylglucosaminyltransferase-like protein, MEK1/2, Tumor, Ras-1, Prp4 protein kinase activity, Mutations, ras, c-ras2, LeMPK3, ATP-protein transphosphorylase activity, Biological, p44mpk, ATP:protein phosphotransferase (non-specific) activity, Line, symptoms, Dp38, Kinase, myd, SAPK2, SEM, Sem, treatment, MAP-k, like-acetylglucosaminyltransferase, Genomes, pp42, MAPK-ERK Kinases, proportionality to, Mbp-1, Dsor2, Evolution, sem, DSor1, DSOR1, allergic reaction, Map Kinase, Map Kinase Kinase, high frequency, sample, Homo sapiens disease, CG1799, Tumors, ERK-A, p82 kinase activity, close to, screening, Neuroblastoma (Schwannian Stroma-Poor), dpERK, dpErk, Viral, Ras2, RAS2, Ras1, RAS1, betaIIPKC, familial, DmMAPK, PMK-2, dp-ERK, PMK-1, Sympathicoblastoma, predicted, PMK-3, Wee-kinase activity, Benign, Recrudescence, Marker, mKIAA0609, dRas85D, MAP Kinase Kinases, pMAPK, pMapK, Chemotherapy, DMEK-1, ras1, ras2, BcDNA:RE36103, EK1-1, fg, DmERKA, rl/MAPK, End Points, proportionality, Hras-1, non-specific serine/threonine protein kinase activity, signs, Benign Neoplasms, rate, Dm Ras1, l(2)41Ac, whole genome, Immunologic, Laboratory Marker, Malignant Neoplasms, Phenotypes, MDC1D, RasI, CT34260, dpERk, enr, MAPK-ERK, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', other neoplasm, Wee 1-like kinase activity, Harvey-ras, Hras1, MAPK Kinases, MEKs, glycogen synthase A kinase activity, chemotherapy, Clinical Marker, Neoplasms, dRas, MAPK-ERK Kinase, Central neuroblastoma, glycogen synthase kinase 3 activity, CG1167, 12559, H-ras, DRAS1, DRas2, IMPDH, LARGE1, LD06825, phosphorylase b kinase kinase activity, EK2-1, Dras2, Dras1, D-Ras, sensitive, Kras-2, disease or disorder, IMPdH, ribosomal protein S6 kinase II activity, Ha-ras, Drug Therapies, MAP, Map, Erk, ERK, Dras, PRKM1, ras 1, PRKM2, protein-serine kinase activity, proportion, Clinical, Recrudescences, MDDGB6, raspberry/impd, STK32, MEK 7, Ras[V12], EK3-4, erk, DRas, Neoplasias, DRas85D/Ras, Dmras64B, protein-cysteine kinase activity, Kinase Kinase, Hpr kinase activity, rll, STK26, SOR, Sor, p38-2, constitutitional genetic, myelin basic protein kinase activity, Biologic, Cancer, findings, Malignant Neoplasm, MAP-ERK, Serum Markers, stress-activated kinase activity, disorders, MAP-2 kinase activity, sor, function, D-ras-1, protein serine kinase activity, Cell, MK, protein phosphokinase activity, Immune Marker, E(faf), near to, DmelCG1167, PKA, PKC, MAPK ERK Kinases, Surrogate End Point, stress-activated protein kinase activity, mapk2, mapk1, Neoplasm, S35097, MEK, Mek, condition, NB, MAP Kinase, protein kinase p58 activity, Biologic Markers, serine/threonine protein kinase activity, RAS85D, Dmras85D, CG12559, l(1)9Eb, Mitogen Activated Protein Kinase Kinases, Surrogate, dpERK1, Endpoints, Specificity, mek, Cancers, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, neuroblastoma NOS (morphologic abnormality), like-glycosyltransferase, (Neuroblastoma NOS) or (sympathicoblastoma), dpMAPK, vicinity of, quotient, hereditary, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, Immune Markers, glycogen synthase kinase activity, Ras1/RAs85D, Biological Markers, Viral Marker, insensitive, protein kinase A activity, dsor1, MAP-ERK Kinase, Mpk2, Mbp1, Biochemical, D-MEK/Dsor, c-rasHa, p42mapk, Endpoint, E(sev)3C, Serum, PRKMK7, CG11485, SR2-1, Laboratory Markers, relapse, Clonal, diseases, kinase-related transforming protein, Su(Raf)34B, diseases and disorders, mitogen-activated protein kinase activity, Relapses, mpk1, D-Ras1, human disease, Erk/Map kinase, RTK, Recurrences, l(1)G0436, DERK-A, ras85B, ras85D, E(sina)7, Rl, neuroblastoma (morphologic abnormality), Raf kinase activity, [M]Neuroblastoma NOS (morphologic abnormality), genetic, MP kinase activity, serine kinase activity, DERK, D-ras-2, Immune, Markers, atypical protein kinase C activity, Viral Markers, disease management, Therapies, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Malignancies, dERK, NB - Neuroblastoma, dSor1, Therapy, Relapse, l(3)s1747, MAP kinase 2 activity, SAPKK4, Surrogate Endpoint, sor/MEK1, gyltl1b-b, Mapk, D-sor-1, Ki-ras, Erk1, DSor, ERK1, ERK2, mapk1a, Biochemical Markers, Biologic Marker, DRODSOR1, M phase-specific cdc2 kinase activity, mapk1b, MapK, MDDGA6, MAPK, Diseases, NOS, p21[Ras1], median, dRas1, dRAS1, KIAA0609, serine protein kinase activity, Dras85D, erk2, Mitogen Activated Protein Kinase Kinase, acetylglucosaminyltransferase-like 1A, mapk, dSor, ras-2, Lines, ERKa, phosphorylase B kinase kinase activity, l(1)G0351, gyltl1b, LD02673, Pharmacotherapy, BcDNA:RE08694, MAP ERK Kinase, resistant, protein glutamyl kinase activity, Neuroblastomas, DmelCG1799, c-Ha-ras, l(2R)EMS45-39, D-ras1, l(1)G0238, D-ras2, mdc1d, DmelCG12559, C-ras1, p38, Dras64B, LARGE_HUMAN, Treatments, C-ras2, l(3)06677, DpErk, DpERK, l(1)G0002, dMEK, ErkA, ERKA, disease, l(1)G0482, hydroxyalkyl-protein kinase activity, WEE1Hu, Patient, Specificity and Sensitivity, c-H-ras, Biochemical Marker, epsilon PKC, l(1)G0127, Dsor, medical condition., inherited genetic, MAPK Kinase, pERK, ribosomal S6 protein kinase activity, other disease, calcium/phospholipid-dependent protein kinase activity, MAPKK7, neuroblastoma, RasV12, GroupII, Clinical Markers, Kras2, Benign Neoplasm, pharmacotherapy, Pharmacotherapies, DmelCG9375, Malignant, froggy, D-mek, Chemotherapies, Gyltl1a, Surrogate End Points, l(1)G0388, Surrogate Markers, Dmek, serine(threonine) protein kinase activity, JNKK2, l(1)G0380, sensitivity, CG15793, T-antigen kinase activity, p21B, galactosyltransferase-associated kinase activity, Somatic, Biomarker, MAPK ERK Kinase, dras1, Dm-ras-64B, MAPKKs, Malignancy, xp42, MKK7, Biological Marker, LARGE, D-sor, l(1)G0391, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, BPFD#36, Ras 85D, protein kinase (phosphorylating) activity, Immunologic Markers, Raf-1, Clients, [M]Neuroblastoma NOS, Sensitivity, disorder, DmERK-A, ras-l, casein kinase (phosphorylating) activity, D-Mek, D-MEK, Immunologic Marker, l(1)G0056, ert1, Mitogen-Activated Protein Kinase Kinase, CG9375, prkm2, prkm1, CT39192, Cell Lines, End Point, K-ras, Client, Somatic Evolution, p38delta, MEK/Dsor1, fs(3)05703, twitchin kinase activity, EP(X)1093, AP50 kinase activity, MBP kinase I activity, AI929937, D-SOR, D-Sor, Xp42, threonine-specific protein kinase activity, DmelCG15793, Serum Marker, MAPKK, frequent, Neuroblastoma, mitogen activated kinase activity, Kinases, Su(Raf)2B, SAPKK-4, EY2-2, Su(tor)3-2, sample population, Surrogate Marker, Drug, D-ERK, Therapeutic, approaches, Treatment, pharmacologic therapy, glycosyltransferase-like protein LARGE1, MAP kinase 1 activity, A-kinase activity"],"additional_accession":[]},"is_claimable":false,"name":"AMC Dept. Oncogenomics","description":"Data Access Committee EGAC00001000321","dates":{"output":"2025-1-9"},"accession":"EGAC00001000321","cross_references":{"TAXONOMY":["9606"],"pubmed":["26121087"],"EGA":["EGAS00001001183","EGAD00001001360"]}}