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Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13)

Panagopoulos, Ioannis LU ; Fioretos, Thoas LU ; Isaksson, Margareth LU ; Samuelsson, Ulf; Billström, Rolf; Strömbeck, Bodil LU ; Mitelman, Felix LU and Johansson, Bertil LU (2001) In Human Molecular Genetics 10(4). p.395-404
Abstract
The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications... (More)
The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
10
issue
4
pages
395 - 404
publisher
Oxford University Press
external identifiers
  • pmid:11157802
  • scopus:0035865032
ISSN
0964-6906
DOI
10.1093/hmg/10.4.395
language
English
LU publication?
yes
id
eb8ec388-f7f1-449b-87f6-79d7de294ff4 (old id 1122210)
date added to LUP
2008-07-09 10:30:26
date last changed
2018-08-12 03:28:18
@article{eb8ec388-f7f1-449b-87f6-79d7de294ff4,
  abstract     = {The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.},
  author       = {Panagopoulos, Ioannis and Fioretos, Thoas and Isaksson, Margareth and Samuelsson, Ulf and Billström, Rolf and Strömbeck, Bodil and Mitelman, Felix and Johansson, Bertil},
  issn         = {0964-6906},
  language     = {eng},
  number       = {4},
  pages        = {395--404},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13)},
  url          = {http://dx.doi.org/10.1093/hmg/10.4.395},
  volume       = {10},
  year         = {2001},
}