title: Complete characterization of the microRNAome in a patient with acute myeloid leukemia.
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.
authors.affiliation: Deparment of Medicine, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Giridharan
authors.initials: G
authors.lastname: Ramsingh
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Koboldt
authors.forename: Maria
authors.initials: M
authors.lastname: Trissal
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Chiappinelli
authors.forename: Todd
authors.initials: T
authors.lastname: Wylie
authors.forename: Sunita
authors.initials: S
authors.lastname: Koul
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chang
authors.forename: Rakesh
authors.initials: R
authors.lastname: Nagarajan
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: Paul
authors.initials: P
authors.lastname: Goodfellow
authors.forename: Vincent
authors.initials: V
authors.lastname: Magrini
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites; D020869:Gene Expression Profiling / Q000379:methods* / Q000639:trends; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D035683:MicroRNAs / Q000032:analysis*; D009154:Mutation; D017423:Sequence Analysis, RNA
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs