Comment[ArrayExpressAccession] E-GEOD-51798 MAGE-TAB Version 1.1 Public Release Date 2014-04-22 Investigation Title Transcriptional dissection of pancreatic tumors engrafted in mice Comment[Submitted Name] Transcriptional dissection of pancreatic tumors engrafted in mice Experiment Description Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published in GEO microarray data. We used PDX models, primary tumors and cell lines from PDAC and hepatocellular carcinoma. All these public data were re-process in order to compare with our 35 samples Term Source Name ArrayExpress EFO Term Source File http://www.ebi.ac.uk/arrayexpress/ http://www.ebi.ac.uk/efo/efo.owl Person Last Name Hidalgo Martínez-García Valencia Hidalgo Person First Name Manuel Raquel Alfonso Manuel Person Email mhidalgo@cnio.es Person Affiliation CNIO Person Phone +34917328000 Person Address Clinical Research Programme, CNIO, C/Melchor Fernandez Almagro 3, Madrid, Madrid, Spain Person Roles submitter Protocol Name P-GSE51798-1 P-GSE51798-3 P-GSE51798-4 P-GSE51798-2 P-GSE51798-5 Protocol Description The data were analyzed with frozenRMA (fRMA) using rma and quantile as background correction and normalization methods. ID_REF = VALUE = fRMA signal intensity Biotinylated cRNA were prepared according to the standard Affymetrix protocol (Expression Analysis Technical Manual, Affymetrix). Following fragmentation, cRNA was hybridized to an Affymetrix Human Genome U133 Plus 2.0 Array. Extraction of total RNA was performed by using Qiagen mini- RNA kit according to the manufacturer's instructions. GeneChips were scanned using the Affymetrix GeneChip Scanner 3000 7G. Protocol Type normalization data transformation protocol labelling protocol hybridization protocol nucleic acid extraction protocol array scanning protocol Experimental Factor Name ORGANISM PART Experimental Factor Type organism part Publication Title Transcriptional dissection of pancreatic tumors engrafted in mice. Publication Author List Martinez-Garcia R, Juan D, Rausell A, Mu�oz M, Ba�os N, Men�ndez C, Lopez-Casas PP, Rico D, Valencia A, Hidalgo M PubMed ID 24739241 Publication DOI 10.1186/gm544 Comment[SecondaryAccession] GSE51798 Comment[GEOReleaseDate] 2014-04-22 Comment[ArrayExpressSubmissionDate] 2013-10-28 Comment[GEOLastUpdateDate] 2014-04-23 Comment[AEExperimentType] transcription profiling by array Comment[AEExperimentType] unknown experiment type Comment[AdditionalFile:Data1] GSE51798_PDX_and_PT_data_plus_reprocessed_data.txt SDRF File E-GEOD-51798.sdrf.txt