title: Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon.
abstract: 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.
authors.affiliation: Jane Anne Nohl Division of Hematology, Department of Medicine, University of Southern California, Los Angeles, CA;
authors.forename: Giridharan
authors.initials: G
authors.lastname: Ramsingh
authors.forename: Meagan A
authors.initials: MA
authors.lastname: Jacoby
authors.forename: Jin
authors.initials: J
authors.lastname: Shao
authors.forename: Rigoberto E
authors.initials: RE
authors.lastname: De Jesus Pizzaro
authors.forename: Dong
authors.initials: D
authors.lastname: Shen
authors.forename: Maria
authors.initials: M
authors.lastname: Trissal
authors.forename: Angela H
authors.initials: AH
authors.lastname: Getz
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walter
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055028:Comparative Genomic Hybridization; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics; D055815:Young Adult
chemical_list: D035683:MicroRNAs