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Introduction  Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations.    Methods  Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer.    Results  Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with  ERBB2  overexpression and 24 with  E-cadherin  gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with  E-cadherin  promoter hypermethylation, which, contrary to  E-cadherin  mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with  p16 INK4   status while only a few miRNAs were associated with  BRCA1, PIK3CA / PTEN  and  TP53  mutation status. Twelve miRNAs were associated with DNA copy number variation of the respective locus.    Conclusion  Luminal-basal and epithelial-mesenchymal associated miRNAs determine the subdivision of miRNA transcriptome of breast cancer cell lines. Specific sets of miRNAs were associated with  ERBB2  overexpression,  p16 INK4a   or  E-cadherin  mutation or  E-cadherin  methylation status, which implies that these miRNAs may contribute to the driver role of these genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of breast cancer cell lines, which can be exploited for functional studies of clinically important miRNAs.

miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs