{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:49:28Z","timestamp":1790167768373,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T00:00:00Z","timestamp":1389744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T00:00:00Z","timestamp":1389744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Roadmap"},{"name":"EuroSyStem and EurocanPlatform"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Human cancers modeled in Genetically Engineered Mouse Models (GEMMs) can provide important mechanistic insights into the molecular basis of tumor development and enable testing of new intervention strategies. The inherent complexity of these models, with often multiple modified tumor suppressor genes and oncogenes, has hampered their use as preclinical models for validating cancer genes and drug targets. In our newly developed approach for the fast generation of tumor cohorts we have overcome this obstacle, as exemplified for three GEMMs; two lung cancer models and one mesothelioma model. Three elements are central for this system; (i) The efficient derivation of authentic Embryonic Stem Cells (ESCs) from established GEMMs, (ii) the routine introduction of transgenes of choice in these GEMM\u2010ESCs by Flp recombinase\u2010mediated integration and (iii) the direct use of the chimeric animals in tumor cohorts. By applying stringent quality controls, the GEMM\u2010ESC approach proofs to be a reliable and effective method to speed up cancer gene assessment and target validation. As proof\u2010of\u2010principle, we demonstrate that\n                    <jats:italic>MycL1<\/jats:italic>\n                    is a key driver gene in Small Cell Lung Cancer.\n                  <\/jats:p>","DOI":"10.1002\/emmm.201303297","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T03:19:44Z","timestamp":1389755984000},"page":"212-225","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Rapid target gene validation in complex cancer mouse models using re\u2010derived embryonic stem cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Ivo J","family":"Huijbers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahmen","family":"Bin Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Cozijnsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Chul","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Proost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Ying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilda","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra","family":"Badhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Krimpenfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa M","family":"Michalak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Berns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,1,15]]},"reference":[{"key":"BFEMMM201303297_CR1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/978-1-4419-7037-4_10","volume":"695","author":"TS Barakat","year":"2010","unstructured":"Barakat TS, Gribnau J (2010) X chromosome inactivation and embryonic stem cells. Adv Exp Med Biol 695: 132\u00a0\u2013\u00a0154","journal-title":"Adv Exp Med Biol"},{"key":"BFEMMM201303297_CR2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/gene.20180","volume":"44","author":"C Beard","year":"2006","unstructured":"Beard C, Hochedlinger K, Plath K, Wutz A, Jaenisch R (2006) Efficient method to generate single\u2010copy transgenic mice by site\u2010specific integration in embryonic stem cells. Genesis 44: 23\u00a0\u2013\u00a028","journal-title":"Genesis"},{"key":"BFEMMM201303297_CR3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nbt787","volume":"21","author":"G Belteki","year":"2003","unstructured":"Belteki G, Gertsenstein M, Ow DW, Nagy A (2003) Site\u2010specific cassette exchange and germline transmission with mouse ES cells expressing phiC31 integrase. Nat Biotechnol 21: 321\u00a0\u2013\u00a0324","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201303297_CR4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1101\/sqb.2005.70.026","volume":"70","author":"J Calbo","year":"2005","unstructured":"Calbo J, Meuwissen R, van Montfort E, van Tellingen O, Berns A (2005) Genotype\u2010phenotype relationships in a mouse model for human small\u2010cell lung cancer. Cold Spring Harb Symp Quant Biol 70: 225\u00a0\u2013\u00a0232","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"BFEMMM201303297_CR5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nmeth.1410","volume":"7","author":"BW Carey","year":"2010","unstructured":"Carey BW, Markoulaki S, Beard C, Hanna J, Jaenisch R (2010) Single\u2010gene transgenic mouse strains for reprogramming adult somatic cells. Nat Methods 7: 56\u00a0\u2013\u00a059","journal-title":"Nat Methods"},{"key":"BFEMMM201303297_CR6","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1101\/gad.2017311","volume":"25","author":"L Chin","year":"2011","unstructured":"Chin L, Hahn WC, Getz G, Meyerson M (2011) Making sense of cancer genomic data. Genes Dev 25: 534\u00a0\u2013\u00a0555","journal-title":"Genes Dev"},{"key":"BFEMMM201303297_CR7","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA et\u00a0al (2013) Multiplex genome engineering using CRISPR\/Cas systems. Science 339: 819\u00a0\u2013\u00a0823","journal-title":"Science"},{"key":"BFEMMM201303297_CR8","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1101\/gad.2046711","volume":"25","author":"AL Dooley","year":"2011","unstructured":"Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, Snyder EL, Senna S, Whittaker CA, Bronson RT et\u00a0al (2011) Nuclear factor I\/B is an oncogene in small cell lung cancer. Genes Dev 25: 1470\u00a0\u2013\u00a01475","journal-title":"Genes Dev"},{"key":"BFEMMM201303297_CR9","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nprot.2011.446","volume":"7","author":"LE Dow","year":"2012","unstructured":"Dow LE, Premsrirut PK, Zuber J, Fellmann C, McJunkin K, Miething C, Park Y, Dickins RA, Hannon GJ, Lowe SW (2012) A pipeline for the generation of shRNA transgenic mice. Nat Protoc 7: 374\u00a0\u2013\u00a0393","journal-title":"Nat Protoc"},{"key":"BFEMMM201303297_CR10","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/nprot.2006.173","volume":"1","author":"GS Eakin","year":"2006","unstructured":"Eakin GS, Hadjantonakis AK (2006) Production of chimeras by aggregation of embryonic stem cells with diploid or tetraploid mouse embryos. Nat Protoc 1: 1145\u00a0\u2013\u00a01153","journal-title":"Nat Protoc"},{"key":"BFEMMM201303297_CR11","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","volume":"31","author":"Y Fu","year":"2013","unstructured":"Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD (2013) High\u2010frequency off\u2010target mutagenesis induced by CRISPR\u2010Cas nucleases in human cells. Nat Biotechnol 31: 822\u00a0\u2013\u00a0826","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201303297_CR12","volume-title":"Manipulating the Mouse Embryo","author":"B Hogan","year":"1994","unstructured":"Hogan B, Beddington R, Costantini F, Lacy E (1994) Manipulating the Mouse Embryo, 2nd edn. Cold Spring Harbour, NY, USA: Cold Spring Harbor Laboratory Press.","edition":"2nd edn"},{"key":"BFEMMM201303297_CR13","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1677\/jme.1.01722","volume":"35","author":"CL Hsieh","year":"2005","unstructured":"Hsieh CL, Xie Z, Liu ZY, Green JE, Martin WD, Datta MW, Yeung F, Pan D, Chung LW (2005) A luciferase transgenic mouse model: visualization of prostate development and its androgen responsiveness in live animals. J Mol Endocrinol 35: 293\u00a0\u2013\u00a0304","journal-title":"J Mol Endocrinol"},{"key":"BFEMMM201303297_CR14","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/bies.201100018","volume":"33","author":"IJ Huijbers","year":"2011","unstructured":"Huijbers IJ, Krimpenfort P, Berns A, Jonkers J (2011) Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse models. BioEssays 33: 701\u00a0\u2013\u00a0710","journal-title":"BioEssays"},{"key":"BFEMMM201303297_CR15","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/gcc.22076","volume":"52","author":"R Iwakawa","year":"2013","unstructured":"Iwakawa R, Takenaka M, Kohno T, Shimada Y, Totoki Y, Shibata T, Tsuta K, Nishikawa R, Noguchi M, Sato\u2010Otsubo A et\u00a0al (2013) Genome\u2010wide identification of genes with amplification and\/or fusion in small cell lung cancer. Genes Chromosom Cancer 52: 802\u00a0\u2013\u00a0816","journal-title":"Genes Chromosom Cancer"},{"key":"BFEMMM201303297_CR16","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1101\/gad.943001","volume":"15","author":"EL Jackson","year":"2001","unstructured":"Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA (2001) Analysis of lung tumor initiation and progression using conditional expression of oncogenic K\u2010ras. Genes Dev 15: 3243\u00a0\u2013\u00a03248","journal-title":"Genes Dev"},{"key":"BFEMMM201303297_CR17","doi-asserted-by":"crossref","first-page":"781","DOI":"10.4161\/cbt.6.5.4005","volume":"6","author":"YH Jeon","year":"2007","unstructured":"Jeon YH, Choi Y, Kang JH, Kim CW, Jeong JM, Lee DS, Chung JK (2007) Immune response to firefly luciferase as a naked DNA. Cancer Biol Ther 6: 781\u00a0\u2013\u00a0786","journal-title":"Cancer Biol Ther"},{"key":"BFEMMM201303297_CR18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ccr.2008.01.030","volume":"13","author":"J Jongsma","year":"2008","unstructured":"Jongsma J, van Montfort E, Vooijs M, Zevenhoven J, Krimpenfort P, van der Valk M, van de Vijver M, Berns A (2008) A conditional mouse model for malignant mesothelioma. Cancer Cell 13: 261\u00a0\u2013\u00a0271","journal-title":"Cancer Cell"},{"key":"BFEMMM201303297_CR19","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ng747","volume":"29","author":"J Jonkers","year":"2001","unstructured":"Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A (2001) Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 29: 418\u00a0\u2013\u00a0425","journal-title":"Nat Genet"},{"key":"BFEMMM201303297_CR20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1387\/ijdb.7981049","volume":"38","author":"E Kawase","year":"1994","unstructured":"Kawase E, Suemori H, Takahashi N, Okazaki K, Hashimoto K, Nakatsuji N (1994) Strain difference in establishment of mouse embryonic stem (ES) cell lines. Int J Dev Biol 38: 385\u00a0\u2013\u00a0390","journal-title":"Int J Dev Biol"},{"key":"BFEMMM201303297_CR21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/35092584","volume":"413","author":"P Krimpenfort","year":"2001","unstructured":"Krimpenfort P, Quon KC, Mooi WJ, Loonstra A, Berns A (2001) Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice. Nature 413: 83\u00a0\u2013\u00a086","journal-title":"Nature"},{"key":"BFEMMM201303297_CR22","doi-asserted-by":"crossref","first-page":"17453","DOI":"10.1073\/pnas.0805638105","volume":"105","author":"Q Liang","year":"2008","unstructured":"Liang Q, Conte N, Skarnes WC, Bradley A (2008) Extensive genomic copy number variation in embryonic stem cells. Proc Natl Acad Sci USA 105: 17453\u00a0\u2013\u00a017456","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201303297_CR23","doi-asserted-by":"crossref","first-page":"7113","DOI":"10.1073\/pnas.1104097108","volume":"108","author":"K McJunkin","year":"2011","unstructured":"McJunkin K, Mazurek A, Premsrirut PK, Zuber J, Dow LE, Simon J, Stillman B, Lowe SW (2011) Reversible suppression of an essential gene in adult mice using transgenic RNA interference. Proc Natl Acad Sci USA 108: 7113\u00a0\u2013\u00a07118","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201303297_CR24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1535-6108(03)00220-4","volume":"4","author":"R Meuwissen","year":"2003","unstructured":"Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A (2003) Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4: 181\u00a0\u2013\u00a0189","journal-title":"Cancer Cell"},{"key":"BFEMMM201303297_CR25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nbt.1755","volume":"29","author":"JC Miller","year":"2011","unstructured":"Miller JC, Tan S, Qiao G, Barlow KA, Wang J, Xia DF, Meng X, Paschon DE, Leung E, Hinkley SJ et\u00a0al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29: 143\u00a0\u2013\u00a0148","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201303297_CR26","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/nm.1996","volume":"15","author":"J Nichols","year":"2009","unstructured":"Nichols J, Jones K, Phillips JM, Newland SA, Roode M, Mansfield W, Smith A, Cooke A (2009) Validated germline\u2010competent embryonic stem cell lines from nonobese diabetic mice. Nat Med 15: 814\u00a0\u2013\u00a0818","journal-title":"Nat Med"},{"key":"BFEMMM201303297_CR27","first-page":"247","volume-title":"Mouse Genetics and Transgenics","author":"A Plagge","year":"2000","unstructured":"Plagge A, Kelsey G, Allen ND (2000) Directed mutagenesis in embryonic stem cells. In Mouse Genetics and Transgenics, Jackson IJ, Abbott CM (eds), Vol. 10, pp 247 \u2013 284. Oxford, UK: Oxford University Press"},{"key":"BFEMMM201303297_CR28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cell.2011.03.012","volume":"145","author":"PK Premsrirut","year":"2011","unstructured":"Premsrirut PK, Dow LE, Kim SY, Camiolo M, Malone CD, Miething C, Scuoppo C, Zuber J, Dickins RA, Kogan SC et\u00a0al (2011) A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 145: 145\u00a0\u2013\u00a0158","journal-title":"Cell"},{"key":"BFEMMM201303297_CR29","doi-asserted-by":"crossref","first-page":"e50081","DOI":"10.1371\/journal.pone.0050081","volume":"7","author":"LG Reinholdt","year":"2012","unstructured":"Reinholdt LG, Howell GR, Czechanski AM, Macalinao DG, Macnicoll KH, Lin CS, Donahue LR, John SW (2012) Generating embryonic stem cells from the inbred mouse strain DBA\/2J, a model of glaucoma and other complex diseases. PLoS One 7: e50081","journal-title":"PLoS One"},{"key":"BFEMMM201303297_CR30","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1101\/gad.12.11.1599","volume":"12","author":"E Robanus\u2010Maandag","year":"1998","unstructured":"Robanus\u2010Maandag E, Dekker M, van der Valk M, Carrozza ML, Jeanny JC, Dannenberg JH, Berns A, te Riele H (1998) p107 is a suppressor of retinoblastoma development in pRb\u2010deficient mice. Genes Dev 12: 1599\u00a0\u2013\u00a01609","journal-title":"Genes Dev"},{"key":"BFEMMM201303297_CR31","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1634\/stemcells.21-1-90","volume":"21","author":"L Schoonjans","year":"2003","unstructured":"Schoonjans L, Kreemers V, Danloy S, Moreadith RW, Laroche Y, Collen D (2003) Improved generation of germline\u2010competent embryonic stem cell lines from inbred mouse strains. Stem Cells 21: 90\u00a0\u2013\u00a097","journal-title":"Stem Cells"},{"key":"BFEMMM201303297_CR32","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1093\/nar\/gkm122","volume":"35","author":"J Seibler","year":"2007","unstructured":"Seibler J, Kleinridders A, Kuter\u2010Luks B, Niehaves S, Bruning JC, Schwenk F (2007) Reversible gene knockdown in mice using a tight, inducible shRNA expression system. Nucleic Acids Res 35: e54","journal-title":"Nucleic Acids Res"},{"key":"BFEMMM201303297_CR33","doi-asserted-by":"crossref","first-page":"7902","DOI":"10.1073\/pnas.1019507108","volume":"108","author":"B Tasic","year":"2011","unstructured":"Tasic B, Hippenmeyer S, Wang C, Gamboa M, Zong H, Chen\u2010Tsai Y, Luo L (2011) Site\u2010specific integrase\u2010mediated transgenesis in mice via pronuclear injection. Proc Natl Acad Sci USA 108: 7902\u00a0\u2013\u00a07907","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMMM201303297_CR34","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nrg2842","volume":"11","author":"FD Urnov","year":"2010","unstructured":"Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11: 636\u00a0\u2013\u00a0646","journal-title":"Nat Rev Genet"},{"key":"BFEMMM201303297_CR35","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2013.04.025","volume":"153","author":"H Wang","year":"2013","unstructured":"Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (2013) One\u2010step generation of mice carrying mutations in multiple genes by CRISPR\/Cas\u2010mediated genome engineering. Cell 153: 910\u00a0\u2013\u00a0918","journal-title":"Cell"},{"key":"BFEMMM201303297_CR36","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature11163","volume":"486","author":"OH Yilmaz","year":"2012","unstructured":"Yilmaz OH, Katajisto P, Lamming DW, Gultekin Y, Bauer\u2010Rowe KE, Sengupta S, Birsoy K, Dursun A, Yilmaz VO, Selig M et\u00a0al (2012) mTORC1 in the Paneth cell niche couples intestinal stem\u2010cell function to calorie intake. Nature 486: 490\u00a0\u2013\u00a0495","journal-title":"Nature"},{"key":"BFEMMM201303297_CR37","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nbt780","volume":"21","author":"QL Ying","year":"2003","unstructured":"Ying QL, Stavridis M, Griffiths D, Li M, Smith A (2003) Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 21: 183\u00a0\u2013\u00a0186","journal-title":"Nat Biotechnol"},{"key":"BFEMMM201303297_CR38","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature06968","volume":"453","author":"QL Ying","year":"2008","unstructured":"Ying QL, Wray J, Nichols J, Batlle\u2010Morera L, Doble B, Woodgett J, Cohen P, Smith A (2008) The ground state of embryonic stem cell self\u2010renewal. Nature 453: 519\u00a0\u2013\u00a0523","journal-title":"Nature"},{"key":"BFEMMM201303297_CR39","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1073\/pnas.0813314106","volume":"106","author":"H Zhu","year":"2009","unstructured":"Zhu H, Acquaviva J, Ramachandran P, Boskovitz A, Woolfenden S, Pfannl R, Bronson RT, Chen JW, Weissleder R, Housman DE et\u00a0al (2009) Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci USA 106: 2712\u00a0\u2013\u00a02716","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["EMBO Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201303297.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/emmm.201303297","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1002\/emmm.201303297\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.1002\/emmm.201303297","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1002\/emmm.201303297.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:08:04Z","timestamp":1779084484000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1002\/emmm.201303297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,15]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2,1]]}},"alternative-id":["BFEMMM201303297"],"URL":"https:\/\/doi.org\/10.1002\/emmm.201303297","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718232328.793489988","asserted-by":"object"}]},"ISSN":["1757-4676","1757-4684"],"issn-type":[{"value":"1757-4676","type":"print"},{"value":"1757-4684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,15]]},"assertion":[{"value":"18 July 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2013","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2013","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}