TY - JOUR
T1 - Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon
AU - Ramsingh, Giridharan
AU - Jacoby, Meagan A.
AU - Shao, Jin
AU - De Jesus Pizzaro, Rigoberto E.
AU - Shen, Dong
AU - Trissal, Maria
AU - Getz, Angela H.
AU - Ley, Timothy J.
AU - Walter, Matthew J.
AU - Link, Daniel C.
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
N2 - Altered microRNA (miRNA) expression is frequently observed in acute myelogenous leukemia (AML) and has been implicated in leukemic transformation. Whether somatic copy number alterations (CNAs) are a frequent cause of altered miRNA gene expression is largely unknown. Herein, we used comparative genomic hybridization with a custom high-resolution miRNA-centric array and/or whole-genome sequence data to identify somatic CNAs involving miRNA genes in 113 cases of AML, including 50 cases of de novo AML, 18 cases of relapsed AML, 15 cases of secondary AML following myelodysplastic syndrome, and 30 cases of therapy-related AML. We identified a total of 48 somatic miRNA gene-containing CNAs that were not identified by routine cytogenetics in 20 patients (18%). All these CNAs also included one or more protein coding genes. We identified a single case with a hemizygous deletion of MIR223, resulting in the complete loss of miR-223 expression. Three other cases of AML were identified with very low to absent miR-223 expression, an miRNA gene known to play a key role in myelopoiesis. However, in these cases, no somatic genetic alteration of MIR223 was identified, suggesting epigenetic silencing. These data show that somatic CNAs specifically targeting miRNA genes are uncommon in AML.
AB - Altered microRNA (miRNA) expression is frequently observed in acute myelogenous leukemia (AML) and has been implicated in leukemic transformation. Whether somatic copy number alterations (CNAs) are a frequent cause of altered miRNA gene expression is largely unknown. Herein, we used comparative genomic hybridization with a custom high-resolution miRNA-centric array and/or whole-genome sequence data to identify somatic CNAs involving miRNA genes in 113 cases of AML, including 50 cases of de novo AML, 18 cases of relapsed AML, 15 cases of secondary AML following myelodysplastic syndrome, and 30 cases of therapy-related AML. We identified a total of 48 somatic miRNA gene-containing CNAs that were not identified by routine cytogenetics in 20 patients (18%). All these CNAs also included one or more protein coding genes. We identified a single case with a hemizygous deletion of MIR223, resulting in the complete loss of miR-223 expression. Three other cases of AML were identified with very low to absent miR-223 expression, an miRNA gene known to play a key role in myelopoiesis. However, in these cases, no somatic genetic alteration of MIR223 was identified, suggesting epigenetic silencing. These data show that somatic CNAs specifically targeting miRNA genes are uncommon in AML.
UR - http://www.scopus.com/inward/record.url?scp=84891520068&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-03-488007
DO - 10.1182/blood-2013-03-488007
M3 - Article
C2 - 24009227
AN - SCOPUS:84891520068
SN - 0006-4971
VL - 122
SP - e44-e51
JO - Blood
JF - Blood
IS - 15
ER -