Double minute chromosomes in acute myeloid leukemia and myelodysplastic syndrome: Identification of new amplification regions by fluorescence in situ hybridization and spectral karyotyping

Double minute chromosomes (dmin) are small chromatin bodies consisting of genes amplified in an extrachromosomal location. dmins are uncommon in hematologic malignancies; they are seen primarily in acute myeloid leukemia, with amplification of the MYC oncogene or, less frequently, the MLL transcription factor. Nine patients with hematologic malignancies with dmin were seen at the Roswell Park Cancer Institute between 1985 and 2000; eight had acute myeloid leukemia and one a myelodysplastic syndrome. Fluorescence in situ hybridization (FISH) demonstrated MYC amplification on dmin in four patients, but MLL amplification was not seen. Spectral karyotyping showed that the dmin derived from chromosome II in one patient and from chromosome I9 in two others without MYC or MLL amplification; derivation from these chromosomes was confirmed by FISH with chromosome paint probes. The dmin of chromosome II origin hybridized to a bacterial artificial chromosome (BAC) RPII-II2M22 that maps to IIq24.3 and is predicted to contain ETSI and other markers, including DIISII35I and DIIS409I. The dmin of chromosome I9 origin in one patient hybridized to BACs RPII-46II2 and RPII-II0JI9; in the other patient, these clones did not hybridize with the dmin, but were found to be amplified on a marker chromosome that was derived from chromosome I9 in that patient's cells. These BACs have been mapped to I9qI2-I9qI3.I and I9qII- I9qI3.I, respectively, and are predicted to contain the markers D I9S409 and DI959I9 and the gene for ubiquinol-cytochrome C reductase, Rieske iron-sulfur polypeptideI (UQCRFSI). dmin originating from chromosome I9 have not been reported previously in hematologic malignancies.