Abstract 3010: The advent of miRNAs in the molecular taxonomy of breast cancer
Authors: Francesca Biagioni, Noa Bossel, Giulia Fontemaggi, Barbara Antoniani, Anna Di Benedetto, Sabrina Strano, Paola Muti, Marcella Mottolese, Eytan Domany, Giovanni Blandino
Journal: Cancer Research (2010)

Abstract Breast cancer (BC) is the most common malignancy in women; worldwide, it is the second most common type of cancer after lung cancer and the fifth most common cause of cancer death. BC progresses as a multi-step process encompassing progressive changes. Although the majority of concepts related to morphologically-defined breast precursor lesions remain valid, molecular genetics and tumor phenotypic characterization have changed the way that the BC multi-step model is viewed. More recently, profiling BC using expression array technology has unravelled a novel molecular taxonomy which classifies BC in three main groups: Luminal, Basal-like and HER2, thereby further extending our knowledge regarding BC biology. microRNA is a new class of small molecules that has been linked to the regulation of proliferation, differentiation, apoptosis and even exocytosis. Accumulating evidence indicates that miRNAs are critical in the control of cell proliferation and survival. In particular, miRNAs show altered expression in cancers, in relation to that shown in normal tissue, which distinguishes cancers arising in different physiological sites. Some miRNAs exhibit differential expression levels in cancer and have demonstrated capability to affect cellular transformation, carcinogenesis and metastasis by acting either as oncogenes or tumor suppressors. Although microRNAs were discovered in humans a mere eight years ago, a host of promising potential applications in the diagnosis, prognoses and therapy of cancer is emerging at a rapid pace. Indeed, specific miRNA expression signatures could have a prognostic value, indicating that miRNAs are determinants of clinical aggressiveness. In this context, newly developed technology like microRNA profiling could have not only the potential to classify tumors but also to predict patient outcome with a high accuracy. In our study we analyzed the three main groups of breast cancer (BC) subtypes: Luminal, Basal-like and HER2. Two biopsies, from the tumor itself and from the peri-tumoral area, were obtained from each patient included in the study. In addition, biopsies from some healthy tissues (reductive mammoplasty) were also analyzed. We extracted RNA using TriZOL reagent and then checked, with the Agilent bioanalyzer, the quality of the samples. We performed the hybridization on Human miRNA Microarray from Agilent that contained probes for 723 human and 76 human viral microRNAs from the Sanger database v.10.1. The bioinformatic analysis revealed distinct groups of miRNAs that were selectively modulated by comparing tumor and peritumoral samples. Experimental work aimed at dissecting the functional role of microRNAs in breast cancer model is in progress. We believe that our work could contribute to a better understanding of the oncogenic potential of a specific subset of miRs and in general help to clarify the role of these microRNAs in the tumorigenic process of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3010.