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MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene

Storlazzi, CT ; Fioretos, Thoas LU ; Surace, C ; Lonoce, A ; Mastrorilli, A ; Strömbeck, Bodil LU ; D'Addabbo, P ; Iacovelli, F ; Minervini, C and Aventin, A , et al. (2006) In Human Molecular Genetics 15(6). p.933-942
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 similar to 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... (More)
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 similar to 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 similar to 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
15
issue
6
pages
933 - 942
publisher
Oxford University Press
external identifiers
  • wos:000235771800011
  • scopus:33644773649
  • pmid:16452126
ISSN
0964-6906
DOI
10.1093/hmg/ddl010
language
English
LU publication?
yes
id
7ae847bd-2dcc-4d37-bdac-f6e0df21203c (old id 416762)
date added to LUP
2016-04-01 12:15:16
date last changed
2021-10-06 01:55:19
@article{7ae847bd-2dcc-4d37-bdac-f6e0df21203c,
  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 similar to 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 similar to 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.},
  author       = {Storlazzi, CT and Fioretos, Thoas and Surace, C and Lonoce, A and Mastrorilli, A and Strömbeck, Bodil and D'Addabbo, P and Iacovelli, F and Minervini, C and Aventin, A and Dastugue, N and Fonatsch, C and Hagemeijer, A and Jotterand, M and Muhlematter, D and Lafage-Pochitaloff, M and Nguyen-Khac, F and Schoch, C and Slovak, ML and Smith, A and Sole, F and Van Roy, N and Johansson, Bertil and Rocchi, M},
  issn         = {0964-6906},
  language     = {eng},
  number       = {6},
  pages        = {933--942},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene},
  url          = {http://dx.doi.org/10.1093/hmg/ddl010},
  doi          = {10.1093/hmg/ddl010},
  volume       = {15},
  year         = {2006},
}