The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations.
Hum Mol Genet
; 19(8): 1507-14, 2010 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-20093295
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 an 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 (one case) and 4q (two 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndromes Mielodisplásicas
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Proteínas Proto-Oncogênicas
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Cromossomos Humanos X
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Proteínas de Ligação a DNA
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Quebras de DNA
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Duplicações Segmentares Genômicas
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Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article