TY - JOUR
T1 - Complete characterization of the microRNAome in a patient with acute myeloid leukemia
AU - Ramsingh, Giridharan
AU - Koboldt, Daniel C.
AU - Trissal, Maria
AU - Chiappinelli, Katherine B.
AU - Wylie, Todd
AU - Koul, Sunita
AU - Chang, Li Wei
AU - Nagarajan, Rakesh
AU - Fehniger, Todd A.
AU - Goodfellow, Paul
AU - Magrini, Vincent
AU - Wilson, Richard K.
AU - Ding, Li
AU - Ley, Timothy J.
AU - Mardis, Elaine R.
AU - Link, Daniel C.
PY - 2010/12/9
Y1 - 2010/12/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650046221&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-05-285395
DO - 10.1182/blood-2010-05-285395
M3 - Article
C2 - 20876853
AN - SCOPUS:78650046221
SN - 0006-4971
VL - 116
SP - 5316
EP - 5326
JO - Blood
JF - Blood
IS - 24
ER -