biostudies-otherNair R3992-4002https://www.ebi.ac.uk/biostudies/studies/S-ECPF-GEOD-43730EurocanPlatformThe HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature and acquisition of a self renewing phenotype independent of an EMT programme or regulation of cancer stem cell markers. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in patibiostudies-othertranscription profiling by arrayEurocanPlatformUnknown33OncogeneHomo sapiensRoden DLPerou CMNair RNaylor MJO'Toole SAShah JSwarbrick AOrmandy CJMcFarland AMorey AYang JHui MKaplan WTeo WSCowley MJNikolic IHerschkowitz JIUsary JLakhani SRSelinger CYe SPfefferle ADBaker LAJunankar SNguyen AArmstrong NfalseA Myc transcriptional program that is independent of EMT drives a poor prognosis tumor-propagating phenotype in HER2+ breast cancerThe HER2 (ERBB2) and MYC genes are commonly amplified genes in breast cancer, yet little is known about their molecular and clinical interaction. Using a novel chimeric mammary transgenic approach and in vitro models, we demonstrate markedly increased self renewal and tumour propagating capability of cells transformed with Her2 and c-Myc. Co-expression of both oncogenes in cultured cells led to a pronounced activation of a c-Myc transcriptional signature and acquisition of a self renewing phenotype independent of an EMT programme or regulation of cancer stem cell markers. We show that HER2 and c-MYC are frequently co-amplified in a clinical breast cancer cohort and that co-amplification is strongly associated with aggressive clinical behaviour and poor outcome. Lastly, we show that in pati2016-04-14T14:20:13Z2014 Jul2016-04-14T14:20:13Z2016-04-14T14:20:13ZS-ECPF-GEOD-43730GSE43730E-GEOD-43730EFO_0000305EFO_0000322E-GEOD-43730