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Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
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2007 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 21, no 10, 2137-2144 p.Article in journal (Refereed) Published
Abstract [en]

Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization (array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60-201,Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq), a similar overexpression was confirmed in t(12,21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12,21)-positive leukemia.

Place, publisher, year, edition, pages
2007. Vol. 21, no 10, 2137-2144 p.
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Natural Sciences
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URN: urn:nbn:se:liu:diva-48488DOI: 10.1038/sj.leu.2404879OAI: oai:DiVA.org:liu-48488DiVA: diva2:269384
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

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Department of Paediatrics in Linköping
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