Human Molecular Genetics Advance Access originally published online on May 26, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Human Molecular Genetics, 2004, Vol. 13, No. 14 1479-1485
DOI: 10.1093/hmg/ddh164
Human Molecular Genetics, Vol. 13, No. 14 © Oxford University Press 2004; all rights reserved
Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies
1Department of Clinical Genetics, University Hospital, 22185 Lund, Sweden, 2Department of Pathological Anatomy and Genetics, Section of Genetics, University of Bari, 70126 Bari, Italy, 3Department of Hematology, University Hospital, 20502 Malmö, Sweden and 4Department of Hematology, University Hospital, 58185 Linköping, Sweden
Received March 15, 2004; Accepted May 13, 2004
Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are found in 
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 generally it has been 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 six cases (five AML and one 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 eight known genes (C8FW, NSE2, POU5FLC20, MYC, PVT1, AK093424, MGC27434 and MLZE). The corresponding region was deleted in one of the chromosome 8 homologues in five of the six 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.
* To whom correspondence should be addressed. Tel: +46 46173369; Fax: +46 46131061; Email: bertil.johansson{at}klingen.lu.se
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Huppi, N. Volfovsky, T. Runfola, T. L. Jones, M. Mackiewicz, S. E. Martin, J. F. Mushinski, R. Stephens, and N. J. Caplen The Identification of MicroRNAs in a Genomically Unstable Region of Human Chromosome 8q24 Mol. Cancer Res., February 1, 2008; 6(2): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Rucker, L. Bullinger, C. Schwaenen, D. B. Lipka, S. Wessendorf, S. Frohling, M. Bentz, S. Miller, C. Scholl, R. F. Schlenk, et al. Disclosure of Candidate Genes in Acute Myeloid Leukemia With Complex Karyotypes Using Microarray-Based Molecular Characterization J. Clin. Oncol., August 20, 2006; 24(24): 3887 - 3894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yao, S. Weremowicz, B. Feng, R. C. Gentleman, J. R. Marks, R. Gelman, C. Brennan, and K. Polyak Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res., April 15, 2006; 66(8): 4065 - 4078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Storlazzi, T. Fioretos, C. Surace, A. Lonoce, A. Mastrorilli, B. Strombeck, P. D'Addabbo, F. Iacovelli, C. Minervini, A. Aventin, et al. MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene Hum. Mol. Genet., March 15, 2006; 15(6): 933 - 942. [Abstract] [Full Text] [PDF]
|
|