Complete characterization of the microRNAome in a patient with acute myeloid leukemia

Giridharan Ramsingh, Daniel C. Koboldt, Maria Trissal, Katherine B. Chiappinelli, Todd Wylie, Sunita Koul, Li Wei Chang, Rakesh Nagarajan, Todd A. Fehniger, Paul Goodfellow, Vincent Magrini, Richard K. Wilson, Li Ding, Timothy J. Ley, Elaine R. Mardis, Daniel C. Link

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and have been implicated in the pathogenesis of cancer. In this study, we applied next generation sequencing techniques to comprehensively assess miRNA expression, identify genetic variants of miRNA genes, and screen for alterations in miRNA binding sites in a patient with acute myeloid leukemia. RNA sequencing of leukemic myeloblasts or CD34+ cells pooled from healthy donors showed that 472 miRNAs were expressed, including 7 novel miRNAs, some of which displayed differential expression. Sequencing of all known miRNA genes revealed several novel germline polymorphisms but no acquired mutations in the leukemia genome. Analysis of the sequence of the 3′-untranslated regions (UTRs) of all coding genes identified a single somatic mutation in the 3′-UTR of TNFAIP2, a known target of the PML-RARα oncogene. This mutation resulted in translational repression of a reporter gene in a Dicer-dependent fashion. This study represents the first complete characterization of the "miRNAome" in a primary human cancer and suggests that generation of miRNA binding sites in the UTR regions of genes is another potential mechanism by which somatic mutations can affect gene expression.

Original languageEnglish
Pages (from-to)5316-5326
Number of pages11
JournalBlood
Volume116
Issue number24
DOIs
StatePublished - Dec 9 2010

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