Comment[ArrayExpressAccession]	E-GEOD-76842
MAGE-TAB Version	1.1						
Public Release Date	2016-01-14
Investigation Title	Suppression of type I interferon signaling overcomes the oncogene-induced senescence and mediates melanoma development and progression						
Comment[Submitted Name]	Suppression of type I interferon signaling overcomes the oncogene-induced senescence and mediates melanoma development and progression
Experiment Description	Activation of oncogenes often leads to induction of the DNA damage responses and onset of the cell senescence. Given that DNA damage can also trigger production of type I interferons (IFN) that contribute to senescence development, we sought to determine the role of IFN in the oncogene-induced senescence. Our data in mouse model demonstrate that inactivation of IFN signaling is sufficient for inducing melanomas in melanocytes harboring mutant Braf. Restoration of IFN signaling in IFN-deficient melanoma cells induces cell senescence and suppresses melanoma progression. In addition, data in human patients that received high dose IFN therapy and in mouse transplanted tumor models strongly suggest the importance of the non-cell-autonomous IFN signaling. Suppression of IFN signaling mediated by the downregulation of IFN receptor IFNAR1 invariably occurs during development of mouse melanoma. Mice harboring the IFNAR1 mutant, which is relatively resistant to downregulation, delay melanoma development, suppress the metastatic disease, and better respond to treatment with BRAF or PD1 inhibitors. These results suggest that IFN signaling is an important tumor suppressive pathway that inhibits melanoma development and progression. Accordingly, the inhibition of IFN pathway via IFNAR1 downregulation plays a key role in melanoma pathogenesis. Conversely, these data also argue for targeting IFNAR1 downregulation to prevent the metastatic disease and improve the efficacy of molecularly targeted and immune-targeted therapies. Two genotypes of mice were examined at 2 to 3 times after tamoxifen adminstration, with 2 replicates for each condition, yielding 8 samples in total.						
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	beiting	Beiting	Fuchs	Katlinskaya	Katlinski		
Person First Name	daniel	Daniel	Serge	Yuliya	Kanstantsin		
Person Email	beiting@vet.upenn.edu						
Person Affiliation	University of Pennsylvania						
Person Address	Pathobiology, University of Pennsylvania, 380 S. University Ave, Philadelphia, PA, USA						
Person Roles	submitter						
Protocol Name	P-GSE76842-1	P-GSE76842-5	P-GSE76842-6	P-GSE76842-2	P-GSE76842-3	P-GSE76842-4	P-GSE76842-7
Protocol Description	The data were quantile normalized without background subtraction using Illumina GenomeStudio V1.8 ID_REF =  VALUE = quantile normalized Detection Pval = 	Biotin labeled complementary RNA (cRNA) was made using the EpiCentre TargetAmp-Nano kit	Standard Illumina hybridization protocol	Topical administration of 4-hydroxytamoxifen (4-HT) of BrafCA; Tyr::CreER; Ifnar1-/- or BrafCA; Tyr::CreER; Ifnar1+/+ mice was performed by preparing 25–50 mg/ml (65–130 mM) solution of 4-HT (70% Z-isomer, Sigma) in dimethylsulphoxide and applying enough solution to wet the right ear, right flank and tail with a small paint brush on postnatal days 2, 3 and 4.	Whole melanomas were recovered at day 20, 38, or 60 post-tamoxifen administration	Tumor samples were dissected from mice after humane euthanasia and processed directly for RNA extraction using the Qiagen miRNeasy kit	Standard Illumina scanning protocol
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol
Experimental Factor Name	time	genotype					
Experimental Factor Type	time	genotype					
Comment[SecondaryAccession]	GSE76842						
Comment[GEOReleaseDate]	2016-01-14						
Comment[ArrayExpressSubmissionDate]	2016-01-13						
Comment[GEOLastUpdateDate]	2016-01-14						
Comment[AEExperimentType]	transcription profiling by array						
Comment[AdditionalFile:Data1]	GSE76842_non-normalized.txt						
SDRF File	E-GEOD-76842.sdrf.txt