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Accession: PRJNA522084 ID: 522084

Comparison of different therapeutic regimens in an INI1-deficient proximal-type epithelioid sarcoma patient-derived xenograft highlights the antitumor activity of the EZH2 inhibitor EPZ-011989 and suggests autophagy as a possible cytoprotective mechanism (human)

See Genome Information for Homo sapiens
We report that differential gene expression analysis of epithelioid sarcoma samples removed from EPZ-011989-treated and untreated mice revealed that, among the 5521 genes with a significant differential expression (according to FDR<0.05), 62% were up-regulated and 38% down-regulated respectively, thus indicating a generally increased transcriptional activity in treated tumors, consistent with EZH2 inhibition. Interestingly, among the top 15 up-regulated genes in the EPZ-011989-treated samples, 8 are involved in cell survival pathways, including autophagy. The induction of autophagy as a fail-safe mechanism against EZH2 inhibition was further validated in the PDX-derived ES-1 cell line by evaluating the effect of autophagy inhibition on drug-induced activity. Overall design: PDX mRNA profiles of untreated and EPZ-011989 treated mice were generated by deep sequencing, in duplicate using Illumina NextSeq 500 Sequencing System
AccessionPRJNA522084; GEO: GSE126495
Data TypeTranscriptome or Gene expression
ScopeMultiisolate
OrganismHomo sapiens[Taxonomy ID: 9606]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens
PublicationsStacchiotti S et al., "Comparative Assessment of Antitumor Effects and Autophagy Induction as a Resistance Mechanism by Cytotoxics and EZH2 Inhibition in INI1-Negative Epithelioid Sarcoma Patient-Derived Xenograft.", Cancers (Basel), 2019 Jul 19;11(7)
SubmissionRegistration date: 13-Feb-2019
AmadeoLab, DRAST, Fondazione IRCCS - Istituto Nazionale dei Tumori
RelevanceMedical
Project Data:
Resource NameNumber
of Links
Sequence data
SRA Experiments4
Publications
PubMed1
PMC1
Other datasets
BioSample4
GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Supplementary Mbytes1
SRA Data Details
ParameterValue
Data volume, Gbases39
Data volume, Mbytes15048

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