MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene. Storlazzi, C. T., Fioretos, T., Surace, C., Lonoce, A., Mastrorilli, A., Strömbeck, B., DAddabbo, P., Iacovelli, F., Minervini, C., Aventin, A., Dastugue, N., Fonatsch, C., Hagemeijer, A., Jotterand, M., Mühlematter, D., Lafage-Pochitaloff, M., Nguyen-Khac, F., Schoch, C., Slovak, M. L, Smith, A., Solè, F., Roy, N. V., Johansson, B., & Rocchi, M. Human molecular genetics, 15(6):933--42, March, 2006.
MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene. [link]Paper  abstract   bibtex   
Double minutes (dmin)-circular, extra-chromosomal amplifications of specific acentric DNA fragments-are relatively frequent in malignant disorders, particularly in solid tumors. In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), dmin are observed in approximately 1% of the cases. Most of them consist of an amplified segment from chromosome band 8q24, always including the MYC gene. Besides this information, little is known about their internal structure. We have characterized in detail the genomic organization of 32 AML and two MDS cases with MYC-containing dmin. The minimally amplified region was shown to be 4.26 Mb in size, harboring five known genes, with the proximal and the distal amplicon breakpoints clustering in two regions of approximately 500 and 600 kb, respectively. Interestingly, in 23 (68%) of the studied cases, the amplified region was deleted in one of the chromosome 8 homologs at 8q24, suggesting excision of a DNA segment from the original chromosomal location according to the 'episome model'. In one case, sequencing of both the dmin and del(8q) junctions was achieved and provided definitive evidence in favor of the episome model for the formation of dmin. Expression status of the TRIB1 and MYC genes, encompassed by the minimally amplified region, was assessed by northern blot analysis. The TRIB1 gene was found over-expressed in only a subset of the AML/MDS cases, whereas MYC, contrary to expectations, was always silent. The present study, therefore, strongly suggests that MYC is not the target gene of the 8q24 amplifications.
@article{ Storlazzi2006,
  author    = {Clelia Tiziana Storlazzi and Thoas Fioretos and Cecilia Surace and Angelo Lonoce and Angela Mastrorilli and Bodil Strömbeck and Pietro DAddabbo and Francesco Iacovelli and Crescenzio Minervini and Anna Aventin and Nicole Dastugue and Christa Fonatsch and Anne Hagemeijer and Martine Jotterand and Dominique Mühlematter and Marina Lafage-Pochitaloff and Florence Nguyen-Khac and Claudia Schoch and Marilyn L Slovak and Arabella Smith and Francesc Solè and Nadine Van Roy and Bertil Johansson and Mariano Rocchi},
  title     = {MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene.},
  journal   = {Human molecular genetics}, 
  abstract   = {Double minutes (dmin)-circular, extra-chromosomal amplifications of specific acentric DNA fragments-are relatively frequent in malignant disorders, particularly in solid tumors. In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), dmin are observed in approximately 1\% of the cases. Most of them consist of an amplified segment from chromosome band 8q24, always including the MYC gene. Besides this information, little is known about their internal structure. We have characterized in detail the genomic organization of 32 AML and two MDS cases with MYC-containing dmin. The minimally amplified region was shown to be 4.26 Mb in size, harboring five known genes, with the proximal and the distal amplicon breakpoints clustering in two regions of approximately 500 and 600 kb, respectively. Interestingly, in 23 (68\%) of the studied cases, the amplified region was deleted in one of the chromosome 8 homologs at 8q24, suggesting excision of a DNA segment from the original chromosomal location according to the 'episome model'. In one case, sequencing of both the dmin and del(8q) junctions was achieved and provided definitive evidence in favor of the episome model for the formation of dmin. Expression status of the TRIB1 and MYC genes, encompassed by the minimally amplified region, was assessed by northern blot analysis. The TRIB1 gene was found over-expressed in only a subset of the AML/MDS cases, whereas MYC, contrary to expectations, was always silent. The present study, therefore, strongly suggests that MYC is not the target gene of the 8q24 amplifications.},
  issn   = {0964-6906},
  month   = {March},
  pages   = {933--42},
  volume   = {15},
  number   = {6},
  url   = {http://www.ncbi.nlm.nih.gov/pubmed/16452126} ,
  year   = {2006}
}
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