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Characterisation of genomic translocation breakpoints and identification of an alternative TCF3/PBX1 fusion transcript in t(1;19)(q23;p13)-positive acute lymphoblastic leukaemias.

Paulsson, Kajsa LU ; Jonson, Tord LU ; Øra, Ingrid LU ; Olofsson, Tor LU ; Panagopoulos, Ioannis LU and Johansson, Bertil LU (2007) In British Journal of Haematology 138(2). p.196-201
Abstract
The t(1;19)(q23; p13), one of the most common translocations in childhoodand adult acute lymphoblastic leukaemias (ALLs), usually results in fusion of exons 1-16 of TCF3 (previously E2A) and exons 3-9 of PBX1. However, some t(1;19)-positive ALLs are negative for this chimaera. We here report an alternative TCF3/PBX1 transcript, fusing exon 17 of TCF3 with exon 5 of PBX1, in a paediatric t(1;19)-positive ALL. The different breakpoints made this hybrid undetectable by reverse transcription polymerase chain reaction using standard TCF3 and PBX1 primers. Hence, ALLs with t(1;19) that test negative for TCF3/PBX1 should be analysed further before excluding this alternative fusion. Furthermore, we have characterised the genomic translocation... (More)
The t(1;19)(q23; p13), one of the most common translocations in childhoodand adult acute lymphoblastic leukaemias (ALLs), usually results in fusion of exons 1-16 of TCF3 (previously E2A) and exons 3-9 of PBX1. However, some t(1;19)-positive ALLs are negative for this chimaera. We here report an alternative TCF3/PBX1 transcript, fusing exon 17 of TCF3 with exon 5 of PBX1, in a paediatric t(1;19)-positive ALL. The different breakpoints made this hybrid undetectable by reverse transcription polymerase chain reaction using standard TCF3 and PBX1 primers. Hence, ALLs with t(1;19) that test negative for TCF3/PBX1 should be analysed further before excluding this alternative fusion. Furthermore, we have characterised the genomic translocation breakpoints in eight TCF3/PBX1-positive ALLs; four cases with a balanced t(1;19) and four with an unbalanced der(19) t(1;19). It has previously been suggested that the breakpoints are clustered, particularly in TCF3, and that N-nucleotides are frequently present in the fusion junctions. Three of seven investigated TCF3 intron 16 breakpoints were within the previously described 14 base pair-cluster, and all but two junctions harboured N-nucleotides. The PBX1 breakpoints were more dispersed, although still clustered in two regions. This confirms that most t(1;19) rearrangements may arise by a combination of illegitimate V(D)J recombination and nonhomologous end joining. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TCF3, acute lymphoblastic leukaemia, genomic breakpoint, PBX1
in
British Journal of Haematology
volume
138
issue
2
pages
196 - 201
publisher
Wiley-Blackwell
external identifiers
  • wos:000247475800008
  • scopus:34250835965
  • pmid:17593026
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2007.06644.x
language
English
LU publication?
yes
id
f4885a74-d75c-4310-87ea-4836843f5c07 (old id 539572)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17593026&dopt=Abstract
date added to LUP
2016-04-01 12:19:07
date last changed
2022-03-21 02:28:27
@article{f4885a74-d75c-4310-87ea-4836843f5c07,
  abstract     = {{The t(1;19)(q23; p13), one of the most common translocations in childhoodand adult acute lymphoblastic leukaemias (ALLs), usually results in fusion of exons 1-16 of TCF3 (previously E2A) and exons 3-9 of PBX1. However, some t(1;19)-positive ALLs are negative for this chimaera. We here report an alternative TCF3/PBX1 transcript, fusing exon 17 of TCF3 with exon 5 of PBX1, in a paediatric t(1;19)-positive ALL. The different breakpoints made this hybrid undetectable by reverse transcription polymerase chain reaction using standard TCF3 and PBX1 primers. Hence, ALLs with t(1;19) that test negative for TCF3/PBX1 should be analysed further before excluding this alternative fusion. Furthermore, we have characterised the genomic translocation breakpoints in eight TCF3/PBX1-positive ALLs; four cases with a balanced t(1;19) and four with an unbalanced der(19) t(1;19). It has previously been suggested that the breakpoints are clustered, particularly in TCF3, and that N-nucleotides are frequently present in the fusion junctions. Three of seven investigated TCF3 intron 16 breakpoints were within the previously described 14 base pair-cluster, and all but two junctions harboured N-nucleotides. The PBX1 breakpoints were more dispersed, although still clustered in two regions. This confirms that most t(1;19) rearrangements may arise by a combination of illegitimate V(D)J recombination and nonhomologous end joining.}},
  author       = {{Paulsson, Kajsa and Jonson, Tord and Øra, Ingrid and Olofsson, Tor and Panagopoulos, Ioannis and Johansson, Bertil}},
  issn         = {{0007-1048}},
  keywords     = {{TCF3; acute lymphoblastic leukaemia; genomic breakpoint; PBX1}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{196--201}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{British Journal of Haematology}},
  title        = {{Characterisation of genomic translocation breakpoints and identification of an alternative TCF3/PBX1 fusion transcript in t(1;19)(q23;p13)-positive acute lymphoblastic leukaemias.}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2141.2007.06644.x}},
  doi          = {{10.1111/j.1365-2141.2007.06644.x}},
  volume       = {{138}},
  year         = {{2007}},
}