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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/539572
- author
- Paulsson, Kajsa
LU
; Jonson, Tord
LU
; Øra, Ingrid
LU
; Olofsson, Tor
LU
; Panagopoulos, Ioannis
LU
and Johansson, Bertil
LU
- organization
- publishing date
- 2007
- 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
- John Wiley & Sons Inc.
- 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
- 2025-04-04 14:40:54
@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 = {{John Wiley & Sons Inc.}},
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}},
}