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The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations.

Paulsson, Kajsa LU ; Haferlach, Claudia; Fonatsch, Christa; Hagemeijer, Anne; Klarskov Andersen, Mette; Slovak, Marilyn L and Johansson, Bertil LU (2010) In Human Molecular Genetics 19. p.1507-1514
Abstract
Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns of additional aberrations. We here present a SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the... (More)
Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns of additional aberrations. We here present a SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the inactive X chromosomes in five cases and of the active in two. The ABCB7 gene, mutated in X-linked sideroblastic anemia and spinocerebellar ataxia, is in the deleted region, suggesting that loss of this gene underlies the frequent presence of ringed sideroblasts. Additional genetic abnormalities were present in 12/14 (86%), including partial uniparental disomies for 9p (1 case) and 4q (2 cases) associated with homozygous mutations of JAK2 and TET2, respectively. In total, TET2 mutations were seen in 4/11 (36%) analyzed cases, thus constituting a common secondary event in idic(X)-positive malignancies. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
19
pages
1507 - 1514
publisher
Oxford University Press
external identifiers
  • wos:000276544000011
  • pmid:20093295
  • scopus:77952299670
ISSN
0964-6906
DOI
10.1093/hmg/ddq024
language
English
LU publication?
yes
id
812d6933-488b-464d-bd96-a2a7ad49b081 (old id 1540679)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20093295?dopt=Abstract
date added to LUP
2010-02-03 10:53:49
date last changed
2018-05-29 09:51:25
@article{812d6933-488b-464d-bd96-a2a7ad49b081,
  abstract     = {Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns of additional aberrations. We here present a SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the inactive X chromosomes in five cases and of the active in two. The ABCB7 gene, mutated in X-linked sideroblastic anemia and spinocerebellar ataxia, is in the deleted region, suggesting that loss of this gene underlies the frequent presence of ringed sideroblasts. Additional genetic abnormalities were present in 12/14 (86%), including partial uniparental disomies for 9p (1 case) and 4q (2 cases) associated with homozygous mutations of JAK2 and TET2, respectively. In total, TET2 mutations were seen in 4/11 (36%) analyzed cases, thus constituting a common secondary event in idic(X)-positive malignancies.},
  author       = {Paulsson, Kajsa and Haferlach, Claudia and Fonatsch, Christa and Hagemeijer, Anne and Klarskov Andersen, Mette and Slovak, Marilyn L and Johansson, Bertil},
  issn         = {0964-6906},
  language     = {eng},
  pages        = {1507--1514},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations.},
  url          = {http://dx.doi.org/10.1093/hmg/ddq024},
  volume       = {19},
  year         = {2010},
}