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Vol. 119, No. 1-2, 2007
Issue release date: December 2007
Cytogenet Genome Res 119:53–59 (2007)

Double minutes (dmin) and homogeneously staining regions (hsr) in myeloid disorders: a new case suggesting that dmin form hsr in vivo

Reddy K.S.
Genzyme Genetics, New York, NY (USA)

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We describe a case of an 87-year-old woman with myelodysplastic syndrome (MDS) in transformation. At presentation, the patient suffered from refractory anemia with excess of blasts (RAEB). The karyotype showed a clone with 3 to >20 double minutes (dmin) that were MYC-positive and, in addition, a cryptic deletion of MYC on one of the chromosome 8 homologs. The dmin varied both in size and in fluorescence intensity for the MYC probe following FISH. After six months, the disease had progressed to refractory anemia with excess of blasts in transformation (RAEBT). The corresponding karyotype showed a second cell line with two markers that appeared like rings and, again, a cryptic MYC deletion on one of the chromosome 8 homologs. The markers contained centromeres and amplified MYC sequences. The deletion of MYC on one of the chromosome 8 homologs and the variable sizes and intensities of the dmin supports an episome model for dmin formation. Chronologically, the MYC-positive dmin appeared first, followed by the appearance of MYC-positive marker chromosomes, suggesting that the dmin may have evolved to form homogeneously staining regions (hsr) in vivo.

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  1. Albertson DG, Collins C, McCormick F, Gray JW: Chromosome aberrations in solid tumors. Nat Genet 34:369–376 (2003).
  2. Amati B, Frank SR, Donjerkovic D, Taubert S: Function of the c-Myc oncoprotein in chromatin remodeling and transcription. Biochim Biophys Acta 1471:135–145 (2001).
  3. Barker PE, Drwinga HL, Hittelman WN, Maddox AM: Double minutes replicate once during S phase of the cell cycle. Exp Cell Res 130:353–360 (1980).
  4. Blackwood EM, Eisenman RN: Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251:1211–1217 (1991).
  5. Carroll SM, Gaudray P, De Rose ML, Emery JF, Meinkoth JL, et al: Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin. Mol Cell Biol 7:1740–1750 (1987).
  6. Carroll SM, DeRose ML, Gaudray P, Moore CM, Needham V, et al: Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol Cell Biol 8:1525–1533 (1988).
  7. Carroll SM, DeRose ML, Kolman JL, Nonet GH, Kelly RE, Wahl GM: Localization of a bidirectional DNA replication origin in the native locus and in episomally amplified murine adenosine deaminase loci. Mol Cell Biol 13:2971–2981 (1993).
  8. Cox D, Yuncken C, Spriggs AI: Minute chromatin bodies in malignant tumors of childhood. Lancet 62:55–58 (1965).

    External Resources

  9. Eckhardt SG, Dai A, Davidson KK, Forseth BJ, Wahl GM, Von Hoff DD: Induction of differentiation in HL60 cells by the reduction of extrachromosomally amplified c-myc. Proc Natl Acad Sci USA 91:6674–6678 (1991).

    External Resources

  10. Gaubatz W: Extrachromosomal circular DNAs and genomic sequence plasticity in eukaryotic cells. Mutat Res 237:271–292 (1990).
  11. Hartley SE, Toolis F: Double minute chromosomes in a case of acute myeloblastic leukemia. Cancer Genet Cytogenet 2:275–280 (1980).

    External Resources

  12. Kanda T, Otter M, Wahl GM: Mitotic segregation of viral and cellular acentric extrachromosomal molecules by chromosome tethering. J Cell Sci 114:49–58 (2001).
  13. Kuttler F, Mai S: Formation of non-random extrachromosomal elements during development, differentiation and oncogenesis. Semin Cancer Biol 17:56–64 (2007).
  14. Levan G, Mandahl N, Bregula U, Klein G, Levan A: Double minute chromosomes are not centromeric regions of the host chromosomes. Hereditas 83:83–90 (1976).
  15. Levens DL: Reconstructing MYC. Genes Dev 17:1071–1077 (2003).
  16. Louis BJ, Vermolen Y, Garini IT, Young A, Guffei A, et al: c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus. Proc Natl Acad Sci USA 102:9613–9618 (2005).
  17. Mai S, Mushinski JF: c-Myc-induced genomic instability. J Environ Pathol Toxicol Oncol 22:179–199 (2003).
  18. Mai S, Guffei A, Fest T, Mushinski JF: c-Myc deregulation promotes a complex network of genomic instability, in Li JJ, Li SA, Llombart-Bosch A (eds): Hormonal Carcinogenesis IV, pp 87–97 (Springer Verlag, New York 2005).
  19. Masuda A, Takahashi T: Chromosome instability in human lung cancers: possible underlying mechanisms and potential consequences in the pathogenesis. Oncogene 21:6884–6897 (2002).
  20. Mateyak MK, Obaya AJ, Adachi S, Sedivy JM: Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination. Cell Growth Differ 8:1039–1048 (1997).
  21. McClintock B: Chromosome organization and gene expression. Cold Spring Harbor Symp Quant Biol 16: 13–47 (1951).
  22. Michalova K, Cermak J, Brezinova J, Zemanova Z: Double minute chromosomes in a patient with myelodysplastic syndrome transforming into acute myeloid leukemia. Cancer Genet Cytogenet 109:76–78 (1999).
  23. Mitelman F, Johansson B, Mertens F (eds): Mitelman Database of Chromosome Aberrations in Cancer. ( Mitelman) (2007).
  24. Narayanan V, Mieczkowski PA, Kim HM, Petes TD, Lobachev KS: The pattern of gene amplification is determined by the chromosomal location of hairpin-capped breaks. Cell 125:1283–1296 (2006).
  25. Nesbit CE, Tersak JM, Prochownik EV: MYC oncogenes and human neoplastic disease. Oncogene 18:3004–3016 (1999).
  26. Ohyashiki JH, Ohyashiki K, Miller KB, Cuiffo BP, Sandberg AA: Acute myelomonocytic leukemia with double minute chromosomes and a normal karyotype. Cancer Genet Cytogenet 25:1–6 (1987).
  27. Pelengaris S, Khan M: The many faces of c-MYC. Arch Biochem Biophys 416: 129–136 (2003).
  28. Schimke RT: Gene amplification and methotrexate resistance in cultured animal cells, Harvey Lect 76 1–25 (1980).
  29. Schoenlein PV, Shen DW, Barrett JT, Pastan I, Gottesman MM: Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells. Mol Biol Cell 3:507–520 (1992).
  30. Shimizu N, Shingaki K, Kaneko-Sasaguri Y, Hashizume T, Kanda T: When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Exp Cell Res 302:233–243 (2005).
  31. Stark GR, Wahl GM: Gene amplification. Ann Rev Biochem 53:447–491 (1984).
  32. Storlazzi CT, Fioretos T, Surace C, Lonoce A, Mastrorilli A, 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 15:933–942 (2006).
  33. Von Hoff DD: New mechanisms of gene amplification in drug resistance (the episome model). Cancer Treat Res 57:1–11 (1991).
  34. Von Hoff DD, Needham-VanDevanter DR, Yucel J, Windle BE, Wahl GM: Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules. Proc Natl Acad Sci USA 85:4804–4808 (1988).
  35. Von Hoff DD, McGill JR, Forseth BJ, Davidson KK, Bradley TP, Van Devanter DR: Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity. Proc Natl Acad Sci USA 89:8165–8169 (1992).
  36. Wahl GM: The importance of circular DNA in mammalian gene amplification. Cancer Res 49:1333–1340 (1989).
  37. Wilson A, Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, Oser GM: c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18:2747–2763 (2004).
  38. Windle B, Draper BW, Yin YX, O’Gorman S, Wahl GM: A central role for chromosome breakage in gene amplification, deletion formation, and amplicon integration, Genes Dev 5:160–174 (1991).

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