Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome.

Lundin, Catarina LU ; Hjorth, Lars LU ; Behrendtz, Mikael ; Nordgren, Ann ; Palmqvist, Lars ; Andersen, Mette Klarskov ; Biloglav, Andrea LU ; Forestier, Erik ; Paulsson, Kajsa LU and Johansson, Bertil LU (2012) In Genes, Chromosomes and Cancer 51. p.196-206
Abstract
Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS-related leukemias, such as GATA1 mutations in ML-DS and deregulation of the CRLF2 gene in DS-ALL. Whether microdeletions/microduplications also vary between DS and non-DS cases is presently unclear. To address this issue, we performed single nucleotide polymorphism array analyses of eight pediatric ML-DS and 17 B-cell precursor DS-ALL. In the ML-DS cases, a total of 29 imbalances (20 gains and nine losses) and two partial uniparental isodisomies... (More)
Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS-related leukemias, such as GATA1 mutations in ML-DS and deregulation of the CRLF2 gene in DS-ALL. Whether microdeletions/microduplications also vary between DS and non-DS cases is presently unclear. To address this issue, we performed single nucleotide polymorphism array analyses of eight pediatric ML-DS and 17 B-cell precursor DS-ALL. In the ML-DS cases, a total of 29 imbalances (20 gains and nine losses) and two partial uniparental isodisomies (pUPDs) were detected. None of the 11 small (defined as <10 Mb) imbalances were recurrent, nor were the pUPDs, whereas of the 18 large aberrations, three were recurrent-dup(1q), +8 and +21. In contrast, several frequent changes were identified in the DS-ALL cases, which harbored 82 imbalances (30 gains and 52 losses) and four pUPDs. Of the 40 large changes, 28 were gains and 12 losses, with +X, dup(Xq), dup(1q), del(7p), dup(8q), del(9p), dup(9p), del(12p), dup(17q), and +21 being recurrent. Of the 40 microdeletions identified, several targeted specific genes, with the following being repeatedly deleted: BTG1 and CDKN2A/B (29% of cases), ETV6, IKZF1, PAX5 and SERP2 (18%), and BTLA, INPP4B, P2RY8, and RB1 (12%). Loss of the SERP2 and INPP4B genes, encoding the stress-associated endoplasmic reticulum protein family member 2 and the inositol polyphosphate 4-phosphatase-II, respectively, has previously never been implicated in leukemia. Although deletions of the other genes have been associated with ALL, the high frequency of BTG1 loss is a novel finding. Such deletions may characterize a clinical subgroup of DS-ALL, comprising mainly boys with a high median age. In conclusion, ML-DS and DS-ALL are genetically distinct, with mainly gains in ML-DS and deletions in DS-ALL. Furthermore, DS-ALL is characterized by several recurrent gene deletions, with BTG1 loss being particularly frequent. © 2011 Wiley Periodicals, Inc. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
51
pages
196 - 206
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000297734400009
  • pmid:22072402
  • scopus:83055184186
  • pmid:22072402
ISSN
1045-2257
DOI
10.1002/gcc.20944
language
English
LU publication?
yes
id
8e8ac36a-4eac-4e29-bcb2-0abf3bf1fb57 (old id 2220978)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22072402?dopt=Abstract
date added to LUP
2016-04-04 08:57:05
date last changed
2022-01-29 08:01:16
@article{8e8ac36a-4eac-4e29-bcb2-0abf3bf1fb57,
  abstract     = {{Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS-related leukemias, such as GATA1 mutations in ML-DS and deregulation of the CRLF2 gene in DS-ALL. Whether microdeletions/microduplications also vary between DS and non-DS cases is presently unclear. To address this issue, we performed single nucleotide polymorphism array analyses of eight pediatric ML-DS and 17 B-cell precursor DS-ALL. In the ML-DS cases, a total of 29 imbalances (20 gains and nine losses) and two partial uniparental isodisomies (pUPDs) were detected. None of the 11 small (defined as &lt;10 Mb) imbalances were recurrent, nor were the pUPDs, whereas of the 18 large aberrations, three were recurrent-dup(1q), +8 and +21. In contrast, several frequent changes were identified in the DS-ALL cases, which harbored 82 imbalances (30 gains and 52 losses) and four pUPDs. Of the 40 large changes, 28 were gains and 12 losses, with +X, dup(Xq), dup(1q), del(7p), dup(8q), del(9p), dup(9p), del(12p), dup(17q), and +21 being recurrent. Of the 40 microdeletions identified, several targeted specific genes, with the following being repeatedly deleted: BTG1 and CDKN2A/B (29% of cases), ETV6, IKZF1, PAX5 and SERP2 (18%), and BTLA, INPP4B, P2RY8, and RB1 (12%). Loss of the SERP2 and INPP4B genes, encoding the stress-associated endoplasmic reticulum protein family member 2 and the inositol polyphosphate 4-phosphatase-II, respectively, has previously never been implicated in leukemia. Although deletions of the other genes have been associated with ALL, the high frequency of BTG1 loss is a novel finding. Such deletions may characterize a clinical subgroup of DS-ALL, comprising mainly boys with a high median age. In conclusion, ML-DS and DS-ALL are genetically distinct, with mainly gains in ML-DS and deletions in DS-ALL. Furthermore, DS-ALL is characterized by several recurrent gene deletions, with BTG1 loss being particularly frequent. © 2011 Wiley Periodicals, Inc.}},
  author       = {{Lundin, Catarina and Hjorth, Lars and Behrendtz, Mikael and Nordgren, Ann and Palmqvist, Lars and Andersen, Mette Klarskov and Biloglav, Andrea and Forestier, Erik and Paulsson, Kajsa and Johansson, Bertil}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  pages        = {{196--206}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome.}},
  url          = {{http://dx.doi.org/10.1002/gcc.20944}},
  doi          = {{10.1002/gcc.20944}},
  volume       = {{51}},
  year         = {{2012}},
}