{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina Genome Analyzer II"],"study_type":["Full Genome Sequencing"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00000000074"],"host":["EGA"],"description":["EGA study EGAS00000000074"],"dataset_title":["Title not provided"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["<h4>Background</h4>Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.<h4>Results</h4>In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.<h4>Conclusions</h4>We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual."],"pubmed_title":["Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors."],"pubmed_authors":["Jones Steven Jm SJ, Laskin Janessa J, Li Yvonne Y YY, Griffith Obi L OL, An Jianghong J, Bilenky Mikhail M, Butterfield Yaron S YS, Cezard Timothee T, Chuah Eric E, Corbett Richard R, Fejes Anthony P AP, Griffith Malachi M, Yee John J, Martin Montgomery M, Mayo Michael M, Melnyk Nataliya N, Morin Ryan D RD, Pugh Trevor J TJ, Severson Tesa T, Shah Sohrab P SP, Sutcliffe Margaret M, Tam Angela A, Terry Jefferson J, Thiessen Nina N, Thomson Thomas T, Varhol Richard R, Zeng Thomas T, Zhao Yongjun Y, Moore Richard A RA, Huntsman David G DG, Birol Inanc I, Hirst Martin M, Holt Robert A RA, Marra Marco A MA"],"pubmed_title_synonyms":["Adenocarcinoma, Carcinomas, Carcinoma, Oxyphilic, Transphosphorylases, Adenomas, Adenoma, Basal Cell, Granular Cell Carcinoma, selection process, \"adenocarcinoma\" EXACT [CSP2005:2000-0386], Tubular Adenocarcinoma, Oxyphilic Adenocarcinoma, Cribriform, Tubular Carcinomas, Transphosphorylase, Cribriform Carcinomas, Malignant, ADNOS, \"adenocarcinomas\" EXACT [SNOMEDCT_2005_07_31:189578007], Adenocarcinomas, Tubular Adenocarcinomas, Malignant Adenomas, Phosphotransferases, Granular Cell Adenocarcinomas, \"adenocarcinoma, Tubular, Granular Cell Carcinomas, Malignant Adenoma, \"adenocarcinoma\" EXACT [NCI2004_11_17:C2852], Granular Cell Adenocarcinoma, no subtype (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:35917007], Tubular Carcinoma, Granular Cell, Oxyphilic Adenocarcinomas, \"adenocarcinoma NOS (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:189582009], Kinase, Basal Cell Adenocarcinomas, Kinases., ATP Phosphotransferases, Basal Cell Adenocarcinoma, Phosphotransferase, Cribriform Carcinoma, ATP"],"name_synonyms":["Transphosphorylases, Kinase, Kinases., ATP Phosphotransferases, Transphosphorylase, Phosphotransferase, selection process, Phosphotransferases, ATP"],"pubmed_abstract_synonyms":["DmErk, extracellular signal-regulated kinase activity, PRKBA, pp44mapk, Akt/PKB, Materials, Nucleotide Sequencing, PhrB photolyase activity, SU 011248, Product, Adenomas, Metastasis, DAKT1/PKB, MTC1, neoplasm metastasis, Tumor, AKT1, ADNOS, Prp4 protein kinase activity, Mutations, Klinoril, Donor Artificial Insemination, LeMPK3, Reto, sulindaco, parenchyma of lung, ATP-protein transphosphorylase activity, Chibret, p44mpk, CDA2, Granular Cell Adenocarcinoma, ATP:protein phosphotransferase (non-specific) activity, Dp38, Tubular Carcinoma, 3, NUP96, SAPK2, epithelium, 4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonate, SEM, Sem, drug resistance, Decision-Making, Cribriform Carcinoma, Deep Sequencing, treatment, MAP-k, pp42, Adenoma, Illumina Sequencing, D-ret, BAY 5459085, Dsor2, sem, RacPK, SUPPRESSOR OF AUXIN RESISTANCE 3, medicine, Homo sapiens disease, Tumors, RET, ERK-A, p82 kinase activity, close to, dpERK, dpErk, pulmo, SU11248, betaIIPKC, lung parenchyma, BAY5459085, DmMAPK, PMK-2, dp-ERK, PMK-1, PMK-3, ret, sunitinib, Wee-kinase activity, Novo Sundac, AKT/PKB, Benign, HSCR1, Clinical Decision Making, DmelCG14396, Next-Generation, dipyrimidine photolyase (photosensitive), pMAPK, pMapK, Heterologous Insemination, p-Akt, activation, Carcinomas, DmERKA, Sulindacum, rl/MAPK, Clinoril, Kenalin, Aclin, \"adenocarcinoma\" EXACT [CSP2005:2000-0386], non-specific serine/threonine protein kinase activity, Benign Neoplasms, l(2)41Ac, dAKT/dPKB, PKB/dAKT, Malignant Neoplasms, High Throughput Sequencing, Artificial Insemination, CT34260, dpERk, antagonists and inhibitors, pulmonary, Material, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', 1H-Indene-3-acetic acid, other neoplasm, Wee 1-like kinase activity, RAC-ALPHA, Adenocarcinoma, HD-59, DmelCG4006, glycogen synthase A kinase activity, Salivary Gland, Neoplasms, glycogen synthase kinase 3 activity, number, 12559, 2-Pyridinecarboxamide, High-Throughput DNA, MEN2, protein-containing complex, AID, phosphorylase b kinase kinase activity, Aid, Next-Generation Sequencing, EK2-1, Granular Cell Adenocarcinomas, BAY-673472, CG1061, Deep, Gene Products, Sutent, lung, disease or disorder, no subtype (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:35917007], DmHD-59, ribosomal protein S6 kinase II activity, neoplasm, Medical, aid, Erk, ERK, PRKM1, Insemination, PRKM2, protein-serine kinase activity, Clinical, Tubular Adenocarcinoma, STK32, F23A5.3, Pyrosequencing, Sequencing, erk, Neoplasias, drugs, Granular Cell Carcinomas, protein-cysteine kinase activity, AKT, Akt, HEL-S-284, Hpr kinase activity, Medical Decision Making, Nexavar, rll, STK26, p38-2, cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidene)indene-3-acetic acid, tumor metastasis, myelin basic protein kinase activity, Heterologous, Cancer, Pharmaceuticals, inhibitors, sunitinibum, Products, Malignant Neoplasm, whole blood, akt, Basal Cell, Metastases, Proteins, disorders, sulindac, stress-activated kinase activity, MAP-2 kinase activity, DAkt1, DAKT1, protein serine kinase activity, Cell, DRet, DRET, c-Ret, protein phosphokinase activity, Human Donor, near to, Metastase, PKB, \"adenocarcinoma, MT, PKA, native protein, CWS6, PKC, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, PKB-ALPHA, Neoplasm, Resistance, condition, dRET, dRet, CG4006, Granular Cell, CDHF12, Apo Sulin, Donor, background, Nu-Sulindac, protein kinase p58 activity, Next Generation Sequencing, serine/threonine protein kinase activity, Dakt1, Artificial, (Z)-, primary cancer, RPE, Sorafenib N Oxide, CG12559, Pharmaceutic Preparations, Arp2, increased number, ARP2, Arthrobid, dpERK1, massively-parallel sequencing, Cancers, dsk1, malignant tumor, Malignant Adenomas, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, p. pigmentosa retinae, Sulindal, Gene Proteins, dAkt/PKB, 5-fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-, dpMAPK, SU011248, vicinity of, High Throughput Nucleotide Sequencing, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Pharmaceutical Products, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, Dret, High-Throughput Nucleotide, glycogen synthase kinase activity, protein kinase A activity, determination, Massively-Parallel, selection process, Mpk2, p42mapk, Neoplasm Metastases, protein, pigmented epithelium, cancer metastasis, SR2-1, High-Throughput RNA Sequencing, diseases, \"adenocarcinoma\" EXACT [NCI2004_11_17:C2852], BAY 43-9006, Pharmaceutical Product, kinase-related transforming protein, diseases and disorders, mitogen-activated protein kinase activity, protein aggregate, mpk1, 4-(4-((((4-chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-, Donor Artificial, increased, human disease, Erk/Map kinase, Granular Cell Carcinoma, pigmented retina, DERK-A, Medical Decision-Making, Tubular Carcinomas, E(sina)7, Rl, PKB|Akt, DNA cyclobutane dipyrimidine photolyase activity, Raf kinase activity, MP kinase activity, serine kinase activity, DERK, High Throughput RNA Sequencing, atypical protein kinase C activity, malignant neoplasm, BAY-545-9085, Pharmaceutical, disease management, Therapies, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Malignancies, dERK, RET51, High-Throughput RNA, BAY 545 9085, Therapy, PRE, Carcinoma, MAP kinase 2 activity, dakt, Mapk, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Erk1, High-Throughput DNA Sequencing, ERK1, ERK2, mapk1a, Salivary, l(3)89Bq, Adenocarcinomas, results, Arthrocine, M phase-specific cdc2 kinase activity, CDHR16, PKB/Akt, PKB/AKT, Ion Torrent Sequencing, Tubular, dAkt, dAKT, Gland, retinal pigment, Malignant Adenoma, mapk1b, MapK, MAPK, Massively-Parallel Sequencing, SU-011248, Diseases, Genetic Materials, Sorafenib Tosylate, Pharmaceutic, Ion Torrent, 4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, DAkt, Basal Cell Adenocarcinoma, serine protein kinase activity, retinal pigment layer, erk2, Genetic Material, neoplasms, mapk, PTC, l(3)04226, ERKa, phosphorylase B kinase kinase activity, DPKB, BcDNA:RE08694, protein glutamyl kinase activity, pAkt, l(2R)EMS45-39, DmelCG12559, Cribriform, p38, MEN2A, MEN2B, Treatments, Tubular Adenocarcinomas, Novo-Sundac, DpErk, DpERK, ErkA, disease, ERKA, phr A photolyase activity, hydroxyalkyl-protein kinase activity, WEE1Hu, Dakt, DNA-photoreactivating enzyme, epsilon PKC, SU-11248, BAY 545-9085, dPKB, Cistron, 2-dihydroindolylidenemethyl)-2, MK-231, Tongues, accessory, pERK, DRAC-PK85, other disease, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, High Throughput DNA Sequencing, GroupII, BAY 43 9006, SU 11248, drug susceptibility/resistance, Oxyphilic Adenocarcinoma, Benign Neoplasm, (Z)-5-Fluoro-2-methyl-1-((p-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid, Gene, glossus, photoreactivating enzyme activity, Malignant, MK 231, supernumerary, presence, Illumina, RET-ELE1, Dpkb, Drug resistance., Sorafenib N-Oxide, resistance, serine(threonine) protein kinase activity, stratum pigmentosa retinae, Basal Cell Adenocarcinomas, Massively Parallel Sequencing, Nu Sulindac, T-antigen kinase activity, Drugs, galactosyltransferase-associated kinase activity, tumor cell migration, cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid, Glands, MOS3, BAY 439006, Ion Proton Sequencing, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Genetic, PRECOCIOUS, Malignancy, xp42, inhibiteur, metastasis, Cribriform Carcinomas, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, protein kinase (phosphorylating) activity, inhibidor, Raf-1, Copal, DRAC-PK, High-Throughput, RNA Sequencing, disorder, DmERK-A, HIGM2, Preparation, Sunitinib Malate, casein kinase (phosphorylating) activity, F23A5_3, Oxyphilic, ert1, BAY 673472, Apo-Sulin, protein complex, 5-(5-Fluoro-2-oxo-1, drug, prkm2, prkm1, CT39192, inhibitor, medical condition, Cistrons, CG14396, p38delta, count in organism, MODIFIER OF SNC1, twitchin kinase activity, glandulae salivariae, DNA Sequencing, Protein, AP50 kinase activity, deoxyribonucleic photolyase activity, salivary gland, MBP kinase I activity, D-Akt, Oxyphilic Adenocarcinomas, rare (European definition), Xp42, antagonists, threonine-specific protein kinase activity, akt1, photolyase activity, dAkt1, mitogen activated kinase activity, Su(Raf)2B, DRAC-PK66, response to drug, EY2-2, \"adenocarcinomas\" EXACT [SNOMEDCT_2005_07_31:189578007], introduction, massively parallel sequencing, Protein Gene Products, Drug, present in greater numbers in organism, Preparations, dakt1, D-ERK, High-Throughput Sequencing, Therapeutic, approaches, MK231, PKBalpha, cardinality, Treatment, Lungs, dAKT1, \"adenocarcinoma NOS (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:189582009], assay, RAC, Rac, Ion Proton, RET9, MAP kinase 1 activity, A-kinase activity, Pharmaceutical Preparation"],"description_synonyms":["DmErk, extracellular signal-regulated kinase activity, PRKBA, pp44mapk, Akt/PKB, Materials, PhrB photolyase activity, SU 011248, Product, Adenomas, Metastasis, DAKT1/PKB, MTC1, neoplasm metastasis, Tumor, AKT1, ADNOS, Prp4 protein kinase activity, Mutations, Klinoril, Donor Artificial Insemination, LeMPK3, Reto, sulindaco, parenchyma of lung, ATP-protein transphosphorylase activity, Chibret, p44mpk, CDA2, Granular Cell Adenocarcinoma, ATP:protein phosphotransferase (non-specific) activity, Dp38, Tubular Carcinoma, 3, NUP96, SAPK2, epithelium, 4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonate, SEM, Sem, drug resistance, Decision-Making, Cribriform Carcinoma, treatment, MAP-k, pp42, Adenoma, D-ret, cell process disease, tumor disease, BAY 5459085, Dsor2, sem, RacPK, SUPPRESSOR OF AUXIN RESISTANCE 3, medicine, Homo sapiens disease, protein-coding, Tumors, RET, ERK-A, p82 kinase activity, close to, dpERK, dpErk, pulmo, SU11248, betaIIPKC, lung parenchyma, BAY5459085, DmMAPK, PMK-2, dp-ERK, PMK-1, tumours, PMK-3, ret, sunitinib, Wee-kinase activity, Novo Sundac, AKT/PKB, Benign, HSCR1, Clinical Decision Making, DmelCG14396, dipyrimidine photolyase (photosensitive), pMAPK, pMapK, Heterologous Insemination, p-Akt, activation, Carcinomas, DmERKA, Sulindacum, rl/MAPK, Clinoril, Kenalin, Aclin, \"adenocarcinoma\" EXACT [CSP2005:2000-0386], non-specific serine/threonine protein kinase activity, Benign Neoplasms, l(2)41Ac, dAKT/dPKB, PKB/dAKT, Malignant Neoplasms, Artificial Insemination, CT34260, dpERk, pulmonary, Material, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', 1H-Indene-3-acetic acid, other neoplasm, Wee 1-like kinase activity, RAC-ALPHA, Adenocarcinoma, HD-59, DmelCG4006, glycogen synthase A kinase activity, Salivary Gland, Neoplasms, glycogen synthase kinase 3 activity, number, 12559, 2-Pyridinecarboxamide, MEN2, protein-containing complex, AID, phosphorylase b kinase kinase activity, Aid, NEOPL, EK2-1, Granular Cell Adenocarcinomas, BAY-673472, CG1061, Gene Products, Sutent, lung, disease or disorder, no subtype (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:35917007], DmHD-59, ribosomal protein S6 kinase II activity, neoplasm, Medical, aid, Erk, ERK, PRKM1, Insemination, PRKM2, protein-serine kinase activity, Clinical, Tubular Adenocarcinoma, STK32, F23A5.3, tumour, erk, Neoplasias, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), drugs, Granular Cell Carcinomas, protein-cysteine kinase activity, AKT, Akt, HEL-S-284, Hpr kinase activity, Medical Decision Making, Nexavar, rll, STK26, p38-2, cis-5-Fluoro-2-methyl-1-((p-methylsulfinyl)benzylidene)indene-3-acetic acid, tumor metastasis, myelin basic protein kinase activity, Neoplastic Growth, Heterologous, Cancer, Pharmaceuticals, sunitinibum, Products, Malignant Neoplasm, whole blood, akt, Basal Cell, Metastases, Proteins, disorders, sulindac, stress-activated kinase activity, MAP-2 kinase activity, DAkt1, DAKT1, protein serine kinase activity, Cell, DRet, DRET, c-Ret, protein phosphokinase activity, Human Donor, near to, Metastase, neoplastic growth, PKB, \"adenocarcinoma, MT, PKA, native protein, CWS6, PKC, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, PKB-ALPHA, Neoplasm, Resistance, condition, dRET, dRet, CG4006, Granular Cell, CDHF12, Apo Sulin, Donor, background, Nu-Sulindac, protein kinase p58 activity, serine/threonine protein kinase activity, Dakt1, Artificial, (Z)-, primary cancer, RPE, Sorafenib N Oxide, CG12559, Pharmaceutic Preparations, Arp2, increased number, ARP2, Arthrobid, dpERK1, Cancers, dsk1, disease of cellular proliferation, malignant tumor, Malignant Adenomas, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, p. pigmentosa retinae, Sulindal, Gene Proteins, dAkt/PKB, 5-fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-, dpMAPK, SU011248, vicinity of, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Pharmaceutical Products, protein serine-threonine kinase activity, Neoplasia, NEOPLASMS BENIGN, SAP kinase activity, Dret, glycogen synthase kinase activity, protein kinase A activity, determination, selection process, neoplasia, Mpk2, p42mapk, Neoplasm Metastases, protein, pigmented epithelium, cancer metastasis, SR2-1, diseases, \"adenocarcinoma\" EXACT [NCI2004_11_17:C2852], BAY 43-9006, Pharmaceutical Product, kinase-related transforming protein, diseases and disorders, mitogen-activated protein kinase activity, protein aggregate, mpk1, 4-(4-((((4-chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-, Donor Artificial, increased, human disease, Erk/Map kinase, Granular Cell Carcinoma, neoplasm (disease), pigmented retina, DERK-A, Medical Decision-Making, Tubular Carcinomas, E(sina)7, Rl, PKB|Akt, DNA cyclobutane dipyrimidine photolyase activity, Raf kinase activity, MP kinase activity, serine kinase activity, DERK, atypical protein kinase C activity, malignant neoplasm, BAY-545-9085, Pharmaceutical, disease management, Therapies, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Malignancies, dERK, tumor, RET51, BAY 545 9085, Therapy, PRE, Carcinoma, MAP kinase 2 activity, dakt, Mapk, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Erk1, ERK1, ERK2, mapk1a, Salivary, neoplastic disease, l(3)89Bq, Adenocarcinomas, results, Arthrocine, M phase-specific cdc2 kinase activity, CDHR16, PKB/Akt, PKB/AKT, Tubular, dAkt, dAKT, Gland, retinal pigment, Malignant Adenoma, mapk1b, MapK, MAPK, SU-011248, Diseases, Genetic Materials, Sorafenib Tosylate, Pharmaceutic, 4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, DAkt, Basal Cell Adenocarcinoma, serine protein kinase activity, retinal pigment layer, erk2, Genetic Material, neoplasms, mapk, PTC, l(3)04226, ERKa, phosphorylase B kinase kinase activity, DPKB, BcDNA:RE08694, protein glutamyl kinase activity, pAkt, l(2R)EMS45-39, DmelCG12559, Cribriform, p38, MEN2A, MEN2B, Treatments, Tubular Adenocarcinomas, Novo-Sundac, DpErk, DpERK, ErkA, disease, ERKA, phr A photolyase activity, hydroxyalkyl-protein kinase activity, WEE1Hu, Dakt, DNA-photoreactivating enzyme, epsilon PKC, SU-11248, BAY 545-9085, dPKB, Cistron, 2-dihydroindolylidenemethyl)-2, MK-231, Tongues, accessory, pERK, DRAC-PK85, other disease, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, GroupII, BAY 43 9006, SU 11248, drug susceptibility/resistance, Oxyphilic Adenocarcinoma, Benign Neoplasm, (Z)-5-Fluoro-2-methyl-1-((p-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid, Gene, glossus, photoreactivating enzyme activity, Malignant, MK 231, presence, supernumerary, RET-ELE1, Dpkb, Drug resistance., Sorafenib N-Oxide, resistance, serine(threonine) protein kinase activity, stratum pigmentosa retinae, Basal Cell Adenocarcinomas, Nu Sulindac, T-antigen kinase activity, Drugs, galactosyltransferase-associated kinase activity, tumor cell migration, cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid, Glands, MOS3, BAY 439006, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Genetic, Malignancy, PRECOCIOUS, xp42, metastasis, Cribriform Carcinomas, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, protein kinase (phosphorylating) activity, Raf-1, Copal, DRAC-PK, disorder, DmERK-A, HIGM2, Preparation, Sunitinib Malate, casein kinase (phosphorylating) activity, F23A5_3, Oxyphilic, ert1, BAY 673472, Apo-Sulin, protein complex, 5-(5-Fluoro-2-oxo-1, drug, prkm2, prkm1, CT39192, medical condition, Cistrons, CG14396, p38delta, count in organism, MODIFIER OF SNC1, twitchin kinase activity, glandulae salivariae, Protein, AP50 kinase activity, deoxyribonucleic photolyase activity, salivary gland, MBP kinase I activity, D-Akt, Oxyphilic Adenocarcinomas, rare (European definition), Xp42, threonine-specific protein kinase activity, akt1, photolyase activity, dAkt1, mitogen activated kinase activity, Su(Raf)2B, DRAC-PK66, response to drug, EY2-2, \"adenocarcinomas\" EXACT [SNOMEDCT_2005_07_31:189578007], introduction, Protein Gene Products, Drug, present in greater numbers in organism, Preparations, dakt1, D-ERK, Therapeutic, approaches, MK231, PKBalpha, cardinality, Treatment, Lungs, dAKT1, \"adenocarcinoma NOS (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:189582009], assay, RAC, Rac, RET9, MAP kinase 1 activity, A-kinase activity, Pharmaceutical Preparation"],"additional_accession":[]},"is_claimable":false,"name":"Evolution of an adenomacarcinoma in response to selection by targeted kinase inhibitors","description":"Background - Adenocarcinomas of the tongue are rare and represent the minority (20-25%) of salivary gland tumors affecting the tongue.  We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment. \n                        Results - In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. 1,078 genes exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow.  Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumours and 9 new somatic protein coding mutations. The observed mutations and amplif\n                        ications were  consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways. Conclusions - We conclude that complete genomic characterization of a rare tumour has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist.  These results also provide direct in-vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual.\n                   ","dates":{"updated":"2013-05-22 21:57:51"},"accession":"EGAS00000000074","cross_references":{"TAXONOMY":["9606"],"pubmed":["20696054"],"EGA":["EGAD00000000045","EGAC00000000011"]}}