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The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias

Lilljebjörn, Henrik LU ; Soneson, Charlotte LU ; Andersson, Anna LU ; Heldrup, Jesper LU ; Behrendtz, Mikael; Kawamata, Norihiko; Ogawa, Seishi; Koeffler, H. Phillip; Mitelman, Felix LU and Johansson, Bertil LU , et al. (2010) In Human Molecular Genetics 19(16). p.3150-3158
Abstract
The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however,... (More)
The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q) and +16 as possible early events in the leukemogenic process. (Less)
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Human Molecular Genetics
volume
19
issue
16
pages
3150 - 3158
publisher
Oxford University Press
external identifiers
  • wos:000280280800005
  • scopus:77955061229
ISSN
0964-6906
DOI
10.1093/hmg/ddq224
language
English
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yes
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fc138b86-1e13-4c4a-acd4-f78974b00b35 (old id 1654944)
date added to LUP
2010-08-31 12:35:07
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2018-05-29 10:04:52
@article{fc138b86-1e13-4c4a-acd4-f78974b00b35,
  abstract     = {The ETV6/RUNX1 fusion gene, present in 25% of B-lineage childhood acute lymphoblastic leukemia (ALL), is thought to represent an initiating event, which requires additional genetic changes for leukemia development. To identify additional genetic alterations, 24 ETV6/RUNX1-positive ALLs were analyzed using 500K single nucleotide polymorphism arrays. The results were combined with previously published data sets, allowing us to ascertain genomic copy number aberrations (CNAs) in 164 cases. In total, 45 recurrent CNAs were identified with an average number of 3.5 recurrent changes per case (range 0-13). Twenty-six percent of cases displayed a set of recurrent CNAs identical to that of other cases in the data set. The majority (74%), however, displayed a unique pattern of recurrent CNAs, indicating a large heterogeneity within this ALL subtype. As previously demonstrated, alterations targeting genes involved in B-cell development were common (present in 28% of cases). However, the combined analysis also identified alterations affecting nuclear hormone response (24%) to be a characteristic feature of ETV6/RUNX1-positive ALL. Studying the correlation pattern of the CNAs allowed us to highlight significant positive and negative correlations between specific aberrations. Furthermore, oncogenetic tree models identified ETV6, CDKN2A/B, PAX5, del(6q) and +16 as possible early events in the leukemogenic process.},
  author       = {Lilljebjörn, Henrik and Soneson, Charlotte and Andersson, Anna and Heldrup, Jesper and Behrendtz, Mikael and Kawamata, Norihiko and Ogawa, Seishi and Koeffler, H. Phillip and Mitelman, Felix and Johansson, Bertil and Fontes, Magnus and Fioretos, Thoas},
  issn         = {0964-6906},
  language     = {eng},
  number       = {16},
  pages        = {3150--3158},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {The correlation pattern of acquired copy number changes in 164 ETV6/RUNX1-positive childhood acute lymphoblastic leukemias},
  url          = {http://dx.doi.org/10.1093/hmg/ddq224},
  volume       = {19},
  year         = {2010},
}