TY - JOUR T1 - microRNAs exhibit high frequency genomic alterations in human cancer. JF - Proc Natl Acad Sci U S A Y1 - 2006 A1 - Zhang, Lin A1 - Huang, Jia A1 - Yang, Nuo A1 - Greshock, Joel A1 - Megraw, Molly S A1 - Giannakakis, Antonis A1 - Liang, Shun A1 - Naylor, Tara L A1 - Barchetti, Andrea A1 - Ward, Michelle R A1 - Yao, George A1 - Medina, Angelica A1 - O'brien-Jenkins, Ann A1 - Katsaros, Dionyssios A1 - Hatzigeorgiou, Artemis A1 - Gimotty, Phyllis A A1 - Weber, Barbara L A1 - Coukos, George KW - Breast Neoplasms KW - Female KW - Gene Dosage KW - Gene Expression Profiling KW - Humans KW - MicroRNAs KW - Neoplasms KW - Nucleic Acid Hybridization KW - Oligonucleotide Array Sequence Analysis KW - Ovarian Neoplasms KW - Statistics as Topic AB -

MicroRNAs (miRNAs) are endogenous noncoding RNAs, which negatively regulate gene expression. To determine genomewide miRNA DNA copy number abnormalities in cancer, 283 known human miRNA genes were analyzed by high-resolution array-based comparative genomic hybridization in 227 human ovarian cancer, breast cancer, and melanoma specimens. A high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in ovarian cancer (37.1%), breast cancer (72.8%), and melanoma (85.9%), where copy number alterations observed in >15% tumors were considered significant for each miRNA gene. We identified 41 miRNA genes with gene copy number changes that were shared among the three cancer types (26 with gains and 15 with losses) as well as miRNA genes with copy number changes that were unique to each tumor type. Importantly, we show that miRNA copy changes correlate with miRNA expression. Finally, we identified high frequency copy number abnormalities of Dicer1, Argonaute2, and other miRNA-associated genes in breast and ovarian cancer as well as melanoma. These findings support the notion that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types.

VL - 103 IS - 24 ER -