{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Cancer Genomics"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001003142"],"host":["EGA"],"description":["EGA study EGAS00001003142"],"dataset_title":["NECC WXS"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease."],"pubmed_title":["Comparative genomics of high grade neuroendocrine carcinoma of the cervix."],"pubmed_authors":["Hillman R Tyler RT, Cardnell Robert R, Fujimoto Junya J, Lee Won-Chul WC, Zhang Jianjun J, Byers Lauren A LA, Ramalingam Preetha P, Leitao Mario M, Swisher Elizabeth E, Futreal P Andrew PA, Frumovitz Michael M"],"name_synonyms":["small, dTAF[[II]]230, TAF[[II]]250, d230, Complete Exome Sequencings, Complete Exome, Exome, TAF200, l(3)84Ab, dTAFII250, BG:DS00004.13, TAFII-250, TAF250/230, EfW1, Cell, dTAF230, dmTAF[[II]]230, Exome Sequencing, TAFII250, neuroendocrine carcinoma, reduced, dmTAF1, Taf230, p230, TAF[[II]]250/230, TFIID, Whole Transcriptome, Transcriptome Sequencing, tiny, neuroendocrine cancer., TAF250, Taf[[II]]250, WES, Complete Transcriptome, Taf200, Complete, Complete Transcriptome Sequencing, Exome Sequencings, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, underdeveloped, cel, cell, Complete Exome Sequencing, Whole Transcriptome Sequencing, hypoplasia, Taf1p, TAF[II]250, CG17603, TAF[[II]], Sequencing, dTAF250, Whole Exome, DmelCG17603, Taf250, SR3-5, Whole, NEC, Whole Exome Sequencing, TAF, Transcriptome Sequencings, TAF230, TAF1"],"pubmed_title_synonyms":["Carcinomas, grade 3/4, Neuroendocrine Carcinomas, Genomics, Structural, neuroendocrine carcinoma, Neuroendocrine Carcinoma, NEC, Comparative, Comparative Genomics, Functional, Structural Genomics, Functional Genomics, Neuroendocrine., high grade, neuroendocrine cancer"],"description_synonyms":["Nespl, DmErk, extracellular signal-regulated kinase activity, Canal, pp44mapk, Wfdc14, A4, Tumor, Ectocervix, cancer of cervix, Prp4 protein kinase activity, Mutations, p110-alpha, dmTAF[[II]]230, ras, LeMPK3, parenchyma of lung, Method, ATP-protein transphosphorylase activity, p44mpk, bbl, ATP:protein phosphotransferase (non-specific) activity, Rare Disease., Dp38, Whole Transcriptome, Transcriptome Sequencing, Kinase, SAPK2, SEM, Sem, C-K-RAS, treatment, average, MAP-k, gamma sarcoglycan, Cervical Canal, TFIID TAF250, pp42, BCC7, cel, Comparative Genomics, Tissue, Dsor2, External Os Cervix, procedures, sem, high grade, MCAP, high frequency, ATP Phosphotransferases, Cervix Cancer, C130027O20Rik, Tumors, ERK-A, p82 kinase activity, dTAF[[II]]230, dpERK, dpErk, pulmo, Oat Cell Carcinomas, Exome, betaIIPKC, lung parenchyma, TAF200, DmMAPK, PMK-2, Procedure, dp-ERK, PMK-1, Uterine, PMK-3, Wee-kinase activity, Cervical Cancer, Benign, intermediate cell small cell carcinoma, Uterine Cervical, vesica urinaria, pMAPK, pMapK, sarcoglycan, Detrusor Muscles, simple tissue, bfy, cancer of the cervix, uterine cervix cancer, Carcinomas, grade 3/4, Complete Transcriptome, DmERKA, rl/MAPK, non-specific serine/threonine protein kinase activity, Benign Neoplasms, Gsa, GSA, l(2)41Ac, GPSA, Methodological, surveillance, Malignant Neoplasms, cervix uteri, Rare, CT34260, GSP, dpERk, pulmonary, RASK2, Taf250, 35kD dystrophin-associated glycoprotein, serine-specific protein kinase activity, Skalp, Whole Exome Sequencing, SAPK, HIPK2, Oed-Sml, cytidine 3', bhy, Uterine Cervical Neoplasm, External Os, other neoplasm, Wee 1-like kinase activity, Orphan Diseases, TAF230, PHP1B, PHP1A, tumor of the cervix uteri, Detrusor Urinae, PHP1C, intermediate cell, AHO, glycogen synthase A kinase activity, Neoplasms, glycogen synthase kinase 3 activity, number, 12559, LFS1, phosphorylase b kinase kinase activity, EK2-1, uterine cervix, Structural, lung, Functional, Kras-2, Cervical Neoplasm, MAM, gamma-SG, ribosomal protein S6 kinase II activity, tumor of the Cervix Uteri, neoplasm, Technique, Pi3, Pi6, Erk, ERK, PRKM1, Orphan Disease, PRKM2, protein-serine kinase activity, Complete, Exome Sequencings, dTAF[[II]]250, occurrence, cell, canalis cervicis uteri, K-RAS4B, K-RAS4A, prevalence, STK32, tumour of the cervix uteri, Serpina1c, Sequencing, Cervical Neoplasms, erk, Neoplasias, Study, dTAF250, Whole Exome, protein-cysteine kinase activity, Small Cell Carcinomas, Whole, Hpr kinase activity, rll, MCM, STK26, cervix cancer, p38-2, myelin basic protein kinase activity, Cancer, Malignant Neoplasm, Complete Exome Sequencings, 35 kDa dystrophin-associated glycoprotein, K-RAS2B, K-RAS2A, Small Cell, Endocervical Canal, stress-activated kinase activity, A930027G11Rik, MAP-2 kinase activity, BG:DS00004.13, protein serine kinase activity, c-Ki-ras, Small Cell Carcinoma, Cell, SGCG, Cancer of the Uterine Cervix, protein phosphokinase activity, dTAF230, Exome Sequencing, PKA, CWS5, PKC, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, Neoplasm, TAF[[II]]250/230, outbreaks, protein kinase p58 activity, 5530400H20Rik, serine/threonine protein kinase activity, Taf[[II]]250, cancer of the uterine cervix, NS, CG12559, DMDA1, underdeveloped, cervix of uterus, dpERK1, Cancer of the Cervix, Uterine Cervical Cancer, Cancers, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, small cell carcinoma - intermediate cell, P1, Orphan, P2, caPI3K, P3, CLOVE, dpMAPK, Oedsml, Cervix, neoplasm of uterine cervix, epidemics, Cervical, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, glycogen synthase kinase activity, MGC130048, Wap3, protein kinase A activity, determination, selection process, Mpk2, PI3K, p42mapk, Tp53, SR2-1, Techniques, Gnpas, POH, kinase-related transforming protein, p110alpha, mitogen-activated protein kinase activity, small cell carcinoma, mpk1, k-ras, rask2, cervical canal of uterus, Erk/Map kinase, Complete Exome Sequencing, Whole Transcriptome Sequencing, Nesp, DERK-A, hypoplasia, intermediate cell (morphologic abnormality), Endocervix, E(sina)7, Rl, Galphas, Raf kinase activity, caudal segment of uterus, MP kinase activity, serine kinase activity, DERK, Methodological Studies, atypical protein kinase C activity, disease management, Therapies, MBP kinase II activity, NESP, gamma-sarcoglycan, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Urinary, Malignancies, dERK, MCMTC, ATP, Therapy, Carcinoma, cervix uteri cancer, MAP kinase 2 activity, Genomics, Mapk, Ki-ras, Comparative, frequency, SG-gamma, Erk1, ERK1, ERK2, mapk1a, Functional Genomics, TAFII-250, TAF250/230, results, Cervixes, M phase-specific cdc2 kinase activity, C20orf45, TAFII250, External Os of the Cervix, Endocervical Canals, mapk1b, MapK, MAPK, cervical cancer, p21, NOS, median, serine protein kinase activity, erk2, neoplasms, mapk, Oat Cell Carcinoma, ERKa, phosphorylase B kinase kinase activity, Transphosphorylases, cervical canal, neck of uterus, BcDNA:RE08694, protein glutamyl kinase activity, Nesp55, l(2R)EMS45-39, DmelCG12559, p38, common, gamma (35kDa dystrophin-associated glycoprotein), CG17603, Methodological Study, TAF[[II]], Treatments, morbidity, Detrusor Muscle, DpErk, DpERK, ErkA, ERKA, hydroxyalkyl-protein kinase activity, Uterine Cervical Cancers, WEE1Hu, DMDA, SR3-5, epsilon PKC, P53, p44, bladder, Transcriptome Sequencings, pERK, KI-RAS, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, d230, SGCG_HUMAN, Procedures, GroupII, Complete Exome, Kras2, NS3, p53, Benign Neoplasm, dTAFII250, Malignant, EfW1, presence, TYPE, DAGA4, reduced, dmTAF1, Taf230, 35DAG, Studies, serine(threonine) protein kinase activity, tiny, SCG3, Phosphotransferase, KRAS2, T-antigen kinase activity, KRAS1, TAF250, p21B, galactosyltransferase-associated kinase activity, vesica, WES, Taf200, Gnasxl, Malignancy, Cervical Canal of the Uterus, xp42, Taf1p, Transphosphorylase, Endocervical, p42 mitogen-activated protein kinase activity, CG18732, CERCA, ATP:protein phosphotransferase (MAPKK-activated) activity, cervix, Table, protein kinase (phosphorylating) activity, Trp53, Raf-1, Spi1-6, Uterine Cervical Canal, DmERK-A, TRP53, Cancer of Cervix, Spi1-3, TAF, casein kinase (phosphorylating) activity, Cervix Neoplasm, Uterine Cervical Canals, incidence, uterine cervical neoplasm, small, Disease, ert1, TAF[[II]]250, 6330412C24Rik, Cervix Neoplasms, prkm2, prkm1, CT39192, p110, l(3)84Ab, K-ras, Phosphotransferases, LGMD2C, Xp53, p38delta, count in organism, twitchin kinase activity, Bladder Detrusor Muscles, p230, Oat Cell, AP50 kinase activity, Cervical Cancers, MBP kinase I activity, TFIID, rare (European definition), techniques, AI929937, Xp42, threonine-specific protein kinase activity, Gnas1, cancer of uterine cervix, urocyst, Complete Transcriptome Sequencing, TAF[[II]]230, Bladder, frequent, mitogen activated kinase activity, Kinases, Uterine Cervix, Su(Raf)2B, cervical neoplasm, EY2-2, TAF[II]250, endemics, D-ERK, DmelCG17603, Therapeutic, kras, CFC2, SCARMD2, cardinality, Treatment, Structural Genomics, Lungs, GNAS1, assay, methodology, MAP kinase 1 activity, A-kinase activity, Bladder Detrusor Muscle, TAF1"],"pubmed_abstract_synonyms":["Nespl, DmErk, extracellular signal-regulated kinase activity, Canal, pp44mapk, Wfdc14, A4, Tumor, Ectocervix, cancer of cervix, Prp4 protein kinase activity, Mutations, p110-alpha, dmTAF[[II]]230, ras, LeMPK3, parenchyma of lung, Method, ATP-protein transphosphorylase activity, p44mpk, bbl, ATP:protein phosphotransferase (non-specific) activity, Rare Disease., Dp38, Whole Transcriptome, Transcriptome Sequencing, Kinase, SAPK2, SEM, Sem, C-K-RAS, treatment, average, MAP-k, gamma sarcoglycan, Cervical Canal, TFIID TAF250, pp42, BCC7, cel, Comparative Genomics, Tissue, Dsor2, External Os Cervix, procedures, sem, high grade, MCAP, high frequency, ATP Phosphotransferases, Cervix Cancer, C130027O20Rik, Tumors, ERK-A, p82 kinase activity, dTAF[[II]]230, dpERK, dpErk, pulmo, Oat Cell Carcinomas, Exome, betaIIPKC, lung parenchyma, TAF200, DmMAPK, PMK-2, Procedure, dp-ERK, PMK-1, Uterine, PMK-3, Wee-kinase activity, Cervical Cancer, Benign, intermediate cell small cell carcinoma, Uterine Cervical, vesica urinaria, pMAPK, pMapK, sarcoglycan, Detrusor Muscles, simple tissue, bfy, cancer of the cervix, uterine cervix cancer, Carcinomas, grade 3/4, Complete Transcriptome, DmERKA, rl/MAPK, non-specific serine/threonine protein kinase activity, Benign Neoplasms, Gsa, GSA, l(2)41Ac, GPSA, Methodological, surveillance, Malignant Neoplasms, cervix uteri, Rare, CT34260, GSP, dpERk, pulmonary, RASK2, Taf250, 35kD dystrophin-associated glycoprotein, serine-specific protein kinase activity, Skalp, Whole Exome Sequencing, SAPK, HIPK2, Oed-Sml, cytidine 3', bhy, Uterine Cervical Neoplasm, External Os, other neoplasm, Wee 1-like kinase activity, Orphan Diseases, TAF230, PHP1B, PHP1A, tumor of the cervix uteri, Detrusor Urinae, PHP1C, intermediate cell, AHO, glycogen synthase A kinase activity, Neoplasms, glycogen synthase kinase 3 activity, number, 12559, LFS1, phosphorylase b kinase kinase activity, EK2-1, uterine cervix, Structural, lung, Functional, Kras-2, Cervical Neoplasm, MAM, gamma-SG, ribosomal protein S6 kinase II activity, tumor of the Cervix Uteri, neoplasm, Technique, Pi3, Pi6, Erk, ERK, PRKM1, Orphan Disease, PRKM2, protein-serine kinase activity, Complete, Exome Sequencings, dTAF[[II]]250, occurrence, cell, canalis cervicis uteri, K-RAS4B, K-RAS4A, prevalence, STK32, tumour of the cervix uteri, Serpina1c, Sequencing, Cervical Neoplasms, erk, Neoplasias, Study, dTAF250, Whole Exome, protein-cysteine kinase activity, Small Cell Carcinomas, Whole, Hpr kinase activity, rll, MCM, STK26, cervix cancer, p38-2, myelin basic protein kinase activity, Cancer, Malignant Neoplasm, Complete Exome Sequencings, 35 kDa dystrophin-associated glycoprotein, K-RAS2B, K-RAS2A, Small Cell, Endocervical Canal, stress-activated kinase activity, A930027G11Rik, MAP-2 kinase activity, BG:DS00004.13, protein serine kinase activity, c-Ki-ras, Small Cell Carcinoma, Cell, SGCG, Cancer of the Uterine Cervix, protein phosphokinase activity, dTAF230, Exome Sequencing, PKA, CWS5, PKC, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, Neoplasm, TAF[[II]]250/230, outbreaks, protein kinase p58 activity, 5530400H20Rik, serine/threonine protein kinase activity, Taf[[II]]250, cancer of the uterine cervix, NS, CG12559, DMDA1, underdeveloped, cervix of uterus, dpERK1, Cancer of the Cervix, Uterine Cervical Cancer, Cancers, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, small cell carcinoma - intermediate cell, P1, Orphan, P2, caPI3K, P3, CLOVE, dpMAPK, Oedsml, Cervix, neoplasm of uterine cervix, epidemics, Cervical, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, glycogen synthase kinase activity, MGC130048, Wap3, protein kinase A activity, determination, selection process, Mpk2, PI3K, p42mapk, Tp53, SR2-1, Techniques, Gnpas, POH, kinase-related transforming protein, p110alpha, mitogen-activated protein kinase activity, small cell carcinoma, mpk1, k-ras, rask2, cervical canal of uterus, Erk/Map kinase, Complete Exome Sequencing, Whole Transcriptome Sequencing, Nesp, DERK-A, hypoplasia, intermediate cell (morphologic abnormality), Endocervix, E(sina)7, Rl, Galphas, Raf kinase activity, caudal segment of uterus, MP kinase activity, serine kinase activity, DERK, Methodological Studies, atypical protein kinase C activity, disease management, Therapies, MBP kinase II activity, NESP, gamma-sarcoglycan, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Urinary, Malignancies, dERK, MCMTC, ATP, Therapy, Carcinoma, cervix uteri cancer, MAP kinase 2 activity, Genomics, Mapk, Ki-ras, Comparative, frequency, SG-gamma, Erk1, ERK1, ERK2, mapk1a, Functional Genomics, TAFII-250, TAF250/230, results, Cervixes, M phase-specific cdc2 kinase activity, C20orf45, TAFII250, External Os of the Cervix, Endocervical Canals, mapk1b, MapK, MAPK, cervical cancer, p21, NOS, median, serine protein kinase activity, erk2, neoplasms, mapk, Oat Cell Carcinoma, ERKa, phosphorylase B kinase kinase activity, Transphosphorylases, cervical canal, neck of uterus, BcDNA:RE08694, protein glutamyl kinase activity, Nesp55, l(2R)EMS45-39, DmelCG12559, p38, common, gamma (35kDa dystrophin-associated glycoprotein), CG17603, Methodological Study, TAF[[II]], Treatments, morbidity, Detrusor Muscle, DpErk, DpERK, ErkA, ERKA, hydroxyalkyl-protein kinase activity, Uterine Cervical Cancers, WEE1Hu, DMDA, SR3-5, epsilon PKC, P53, p44, bladder, Transcriptome Sequencings, pERK, KI-RAS, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, d230, SGCG_HUMAN, Procedures, GroupII, Complete Exome, Kras2, NS3, p53, Benign Neoplasm, dTAFII250, Malignant, EfW1, presence, TYPE, DAGA4, reduced, dmTAF1, Taf230, 35DAG, Studies, serine(threonine) protein kinase activity, tiny, SCG3, Phosphotransferase, KRAS2, T-antigen kinase activity, KRAS1, TAF250, p21B, galactosyltransferase-associated kinase activity, vesica, WES, Taf200, Gnasxl, Malignancy, Cervical Canal of the Uterus, xp42, Taf1p, Transphosphorylase, Endocervical, p42 mitogen-activated protein kinase activity, CG18732, CERCA, ATP:protein phosphotransferase (MAPKK-activated) activity, cervix, Table, protein kinase (phosphorylating) activity, Trp53, Raf-1, Spi1-6, Uterine Cervical Canal, DmERK-A, TRP53, Cancer of Cervix, Spi1-3, TAF, casein kinase (phosphorylating) activity, Cervix Neoplasm, Uterine Cervical Canals, incidence, uterine cervical neoplasm, small, Disease, ert1, TAF[[II]]250, 6330412C24Rik, Cervix Neoplasms, prkm2, prkm1, CT39192, p110, l(3)84Ab, K-ras, Phosphotransferases, LGMD2C, Xp53, p38delta, count in organism, twitchin kinase activity, Bladder Detrusor Muscles, p230, Oat Cell, AP50 kinase activity, Cervical Cancers, MBP kinase I activity, TFIID, rare (European definition), techniques, AI929937, Xp42, threonine-specific protein kinase activity, Gnas1, cancer of uterine cervix, urocyst, Complete Transcriptome Sequencing, TAF[[II]]230, Bladder, frequent, mitogen activated kinase activity, Kinases, Uterine Cervix, Su(Raf)2B, cervical neoplasm, EY2-2, TAF[II]250, endemics, D-ERK, DmelCG17603, Therapeutic, kras, CFC2, SCARMD2, cardinality, Treatment, Structural Genomics, Lungs, GNAS1, assay, methodology, MAP kinase 1 activity, A-kinase activity, Bladder Detrusor Muscle, TAF1"],"additional_accession":[]},"is_claimable":false,"name":"Whole exome sequencing of small cell neuroendocrine cancer of the cervix","description":"In order to improve treatment selection for high grade neuroendocrine carcinomas of the cervix (NECC), we performed a comparative genomic analysis between this rare tumor type and other cervical cancer types, as well as extra-cervical neuroendocrine small cell carcinomas of the lung and bladder. We performed whole exome sequencing on fresh-frozen tissue from 15 NECCs and matched normal tissue. We then identified mutations and copy number variants using standard analysis pipelines. Published mutation tables from cervical cancers and extra-cervical small cell carcinomas were used for comparative analysis. Descriptive statistical methods were used and a two-sided threshold of P < .05 was used for significance. In the NECC cohort, we detected a median of 1.7 somatic mutations per megabase (range 1.0-20.9). PIK3CA p.E545K mutations were the most frequency observed oncogenic mutation (4/15 tumors, 27%). Activating MAPK pathway mutations in KRAS (p.G12D) and GNAS (p.R201C) co-occurred in two tumors (13%). In total we identified PI3-kinase or MAPK pathway activating mutations in 67% of NECC. When compared to NECC, lung and bladder small cell carcinomas exhibited a statistically significant higher rate of coding mutations (P < .001 for lung; P = .001 for bladder). Mutation of TP53 was uncommon in NECC (13%) and was more frequent in both lung (103 of 110 tumors [94%], P < .001) and bladder (18 of 19 tumors [95%], P < .001) small cell carcinoma. These comparative genomics data suggest that NECC may be genetically more similar to common cervical cancer subtypes than to extra-cervical small cell neuroendocrine carcinomas of the lung and bladder. These results may have implications for the selection of cytotoxic and targeted therapy regimens for this rare disease.","dates":{"updated":"2020-09-14 11:23:30"},"accession":"EGAS00001003142","cross_references":{"TAXONOMY":["9606"],"pubmed":["32544169"],"EGA":["EGAD00001006391","EGAC00001001731"]}}