Human Molecular Genetics Advance Access published online on May 26, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh164
© 2004 by Oxford University Press
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1 Department of Clinical Genetics, University Hospital, 22185 Lund, Sweden; Department of Pathological Anatomy and Genetics, Section of Genetics, University of Bari, 70126 Bari, Italy
* To whom correspondence should be addressed. E-mail: bertil.Johansson{at}klingen.lu.se.
Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are found in approximately 1% of karyotypically abnormal acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). The MYC gene at 8q24 has been reported to be amplified in the majority of the cases, and it has been generally assumed that MYC is the target gene. However, only a few studies have focused on the extent of the amplicon or on the expression patterns of the amplified genes. We have studied 6 cases (5 AML and 1 MDS) with MYC-containing dmin. Detailed fluorescence in situ hybridization analyses identified a common 4.3 Mb amplicon, with clustered proximal and distal breakpoints, harboring 8 known genes (C8FW, NSE2, POU5FLC20, MYC, PVT1, AK093424, MGC27434, and MLZE). The corresponding region was deleted in one of the chromosome 8 homologues in 5 of the 6 cases, suggesting that the dmin originated through extra replication (or loop-formation)-excision-amplification. Northern blot analysis revealed that MYC was not overexpressed. Instead, the C8FW gene, encoding a phosphoprotein regulated by mitogenic pathways, displayed increased expression. These results exclude MYC as the target gene and indicate that overexpression of C8FW may be the functionally important consequence of 8q24 amplicons in AML and MDS.
Article
Identification of a commonly amplified 4.3 Mb region with overexpression of the C8FW gene, encoding a phosphoprotein regulated by mitogenic pathways, but not of the MYC gene in MYC-containing double minutes in myeloid malignancies
2 Department of Clinical Genetics, University Hospital, 22185 Lund, Sweden
3 Department of Hematology, University Hospital, 20502 Malmö, Sweden
4 Department of Hematology, University Hospital, 58185 Linköping, Sweden
5 Department of Pathological Anatomy and Genetics, Section of Genetics, University of Bari, 70126 Bari, Italy
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