Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome.
Monosomy 7 and interstitial deletions in the long arm of chromosome 7 (-7/7q-) is a common nonrandom chromosomal abnormality found frequently in myeloid disorders including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML). Using a short probe-based microarray comparative genomic hybridization (mCGH) technology, we identified a common microdeletion cluster in 7q21.3 subband, which is adjacent to 'hot deletion region' thus far identified by conventional methods. This common microdeletion cluster contains three poorly characterized genes; Samd9, Samd9L, and a putative gene LOC253012, which we named Miki. Gene copy number assessment of three genes by real-time PCR revealed heterozygous deletion of these three genes in adult patients with AML and MDS at high frequency, in addition to JMML patients. Miki locates to mitotic spindles and centrosomes and downregulation of Miki by RNA interference induced abnormalities in mitosis and nuclear morphology, similar to myelodysplasia. In addition, a recent report indicated Samd9 as a tumor suppressor. These findings indicate the usefulness of the short probe-based CGH to detect microdeletions. The three genes located to 7q21.3 would be candidates for myeloid tumor-suppressor genes on 7q.
Asou
Hiroya
H
Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology & Medicine, Hiroshima University, Hiroshima, Japan.
Matsui
Hirotaka
H
Ozaki
Yuko
Y
Nagamachi
Akiko
A
Nakamura
Megumi
M
Aki
Daisuke
D
Inaba
Toshiya
T
D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000235:genetics*; D008938:Mitosis / Q000235:genetics; D005810:Multigene Family; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D017384:Sequence Deletion
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C514443:SAMD9 protein, human