microRNAs exhibit high frequency genomic alterations in human cancer.

TitlemicroRNAs exhibit high frequency genomic alterations in human cancer.
Publication TypeJournal Article
Year of Publication2006
AuthorsZhang, L, Huang, J, Yang, N, Greshock, J, Megraw, MS, Giannakakis, A, Liang, S, Naylor, TL, Barchetti, A, Ward, MR, Yao, G, Medina, A, O'brien-Jenkins, A, Katsaros, D, Hatzigeorgiou, A, Gimotty, PA, Weber, BL, Coukos, G
JournalProc Natl Acad Sci U S A
Date Published2006 Jun 13
KeywordsBreast Neoplasms, Female, Gene Dosage, Gene Expression Profiling, Humans, MicroRNAs, Neoplasms, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Ovarian Neoplasms, Statistics as Topic

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID16754881
PubMed Central IDPMC1474008
Grant ListP50-CA083638 / CA / NCI NIH HHS / United States
P50-CA093372 / CA / NCI NIH HHS / United States