Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon.

TitleAcquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon.
Publication TypeJournal Article
Year of Publication2013
AuthorsRamsingh G, Jacoby MA, Shao J, De Jesus Pizzaro RE, Shen D, Trissal M, Getz AH, Ley TJ, Walter MJ, Link DC
JournalBlood
Volume122
Issue15
Paginatione44-51
Date Published2013 Oct 10
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.

DOI10.1371/journal.pone.0073023
Alternate JournalBlood