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Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies
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2004 (English)In: Human Molecular Genetics, ISSN 0964-6906, Vol. 13, no 14, 1479-1485 p.Article in journal (Refereed) Published
Abstract [en]

Double minutes (dmin), the cytogenetic hallmark of genomic amplification, are found in ∼1% of karyotypically abnormal acute myelold 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. © Oxford University Press 2004, all rights reserved.

Place, publisher, year, edition, pages
2004. Vol. 13, no 14, 1479-1485 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-24204DOI: 10.1093/hmg/ddh164Local ID: 3797OAI: diva2:244521
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2011-01-12

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Juliusson, Gunnar
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Faculty of Health SciencesOncologyDepartment of Haematology UHL
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