TY - JOUR T1 - Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. JF - Proc Natl Acad Sci U S A Y1 - 2008 A1 - Zhang, Lin A1 - Volinia, Stefano A1 - Bonome, Tomas A1 - Calin, George Adrian A1 - Greshock, Joel A1 - Yang, Nuo A1 - Liu, Chang-Gong A1 - Giannakakis, Antonis A1 - Alexiou, Pangiotis A1 - Hasegawa, Kosei A1 - Johnstone, Cameron N A1 - Megraw, Molly S A1 - Adams, Sarah A1 - Lassus, Heini A1 - Huang, Jia A1 - Kaur, Sippy A1 - Liang, Shun A1 - Sethupathy, Praveen A1 - Leminen, Arto A1 - Simossis, Victor A A1 - Sandaltzopoulos, Raphael A1 - Naomoto, Yoshio A1 - Katsaros, Dionyssios A1 - Gimotty, Phyllis A A1 - DeMichele, Angela A1 - Huang, Qihong A1 - Bützow, Ralf A1 - Rustgi, Anil K A1 - Weber, Barbara L A1 - Birrer, Michael J A1 - Hatzigeorgiou, Artemis G A1 - Croce, Carlo M A1 - Coukos, George KW - DNA, Neoplasm KW - Down-Regulation KW - Epigenesis, Genetic KW - Epithelial Cells KW - Female KW - Gene Expression Profiling KW - Gene Expression Regulation, Neoplastic KW - Genome, Human KW - Humans KW - MicroRNAs KW - Neoplasm Staging KW - Ovarian Neoplasms KW - Ribonuclease III KW - RNA, Messenger KW - Survival Analysis AB -

MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of approximately 15% and at least approximately 36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.

VL - 105 IS - 19 ER -