title: microRNAs exhibit high frequency genomic alterations in human cancer.
abstract: 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.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Nuo
authors.initials: N
authors.lastname: Yang
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Molly S
authors.initials: MS
authors.lastname: Megraw
authors.forename: Antonis
authors.initials: A
authors.lastname: Giannakakis
authors.forename: Shun
authors.initials: S
authors.lastname: Liang
authors.forename: Tara L
authors.initials: TL
authors.lastname: Naylor
authors.forename: Andrea
authors.initials: A
authors.lastname: Barchetti
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Ward
authors.forename: George
authors.initials: G
authors.lastname: Yao
authors.forename: Angelica
authors.initials: A
authors.lastname: Medina
authors.forename: Ann
authors.initials: A
authors.lastname: O'brien-Jenkins
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Artemis
authors.initials: A
authors.lastname: Hatzigeorgiou
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics; D013223:Statistics as Topic
chemical_list: D035683:MicroRNAs