TY - JOUR A1 - Volinia, Stefano A1 - Galasso, Marco A1 - Costinean, Stefan A1 - Tagliavini, Luca A1 - Gamberoni, Giacomo A1 - Drusco, Alessandra A1 - Marchesini, Jlenia A1 - Mascellani, Nicoletta A1 - Sana, Maria Elena A1 - Abu Jarour, Ramzey A1 - Desponts, Caroline A1 - Teitell, Michael A1 - Baffa, Raffaele A1 - Aqeilan, Rami A1 - Iorio, Marilena V. A1 - Taccioli, Cristian A1 - Garzon, Ramiro A1 - Di Leva, Gianpiero A1 - Fabbri, Muller A1 - Catozzi, Marco A1 - Previati, Maurizio A1 - Ambs, Stefan A1 - Palumbo, Tiziana A1 - Garofalo, Michela A1 - Veronese, Angelo A1 - Bottoni, Arianna A1 - Gasparini, Pierluigi A1 - Harris, Curtis C. A1 - Visone, Rosa A1 - Pekarsky, Yuri A1 - de la Chapelle, Albert A1 - Bloomston, Mark A1 - Dillhoff, Mary A1 - Rassenti, Laura Z. A1 - Kipps, Thomas J. A1 - Huebner, Kay A1 - Pichiorri, Flavia A1 - Lenze, Dido A1 - Cairo, Stefano A1 - Buendia, Marie-Annick A1 - Pineau, Pascal A1 - Dejean, Anne A1 - Zanesi, Nicola A1 - Rossi, Simona A1 - Calin, George A. A1 - Liu, Chang-Gong A1 - Palatini, Jeff A1 - Negrini, Massimo A1 - Vecchione, Andrea A1 - Rosenberg, Anne A1 - Croce, Carlo M. T1 - Reprogramming of miRNA networks in cancer and leukemia Y1 - 2010/05/01 JF - Genome Research JO - Genome Research SP - 589 EP - 599 DO - 10.1101/gr.098046.109 VL - 20 IS - 5 UR - http://genome.cshlp.org/content/20/5/589.abstract N2 - We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network. ER -