Document Detail


Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays.
MedLine Citation:
PMID:  18508791     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We undertook a genome wide single nucleotide polymorphism analysis of a spectrum of patients with myelodysplastic syndrome del(5q) in order to investigate whether additional genomic abnormalities occur. Single nucleotide polymorphism array analysis has been shown to detect not only gene deletions but also regions of uniparental disomy that can pinpoint particular regions for mutation analysis. DESIGN AND METHODS: We studied 42 cases of myelodysplastic syndrome with del(5q), comprising 21 patients with 5q- syndrome and 21 with del(5q) (not 5q- syndrome), and 45 healthy controls by genome wide single nucleotide polymorphism analysis with the 50K Affymetrix single nucleotide polymorphism arrays. RESULTS: The del(5q) was characterized in all cases. The commonly deleted region of the 5q- syndrome extends between the genes SH3TC2 (proximal boundary) and GLRA1 (distal boundary) and measures 2.9 Mb. Copy number changes in addition to the del(5q) were observed in 10 of 21 patients with del(5q) myelodysplastic syndrome but in none of the patients with the 5q- syndrome. A total of 63 regions of uniparental disomy greater than 2 Mb were detected in 40 of 42 patients, dispersed on 18/23 chromosomes. In the 5q- syndrome group 31 regions of uniparental disomy were identified in 19 of 21 patients, the largest one being 7.6 Mb. All 21 patients with del(5q) myelodysplastic syndrome had uniparental disomy; in total 32 regions of uniparental disomy were identified in the 21 patients, including six regions of uniparental disomy > 10 Mb. Eight recurrent regions of uniparental disomy were observed among the 42 patients. For eight patients we had T-cell DNA as a germline control and four recurrent regions of uniparental disomy were identified that were present only in the neutrophil and not T-cell DNA. One small region of uniparental disomy at 10p12.31-p12.2 was observed in four patients with the 5q- syndrome. CONCLUSIONS: This study shows that regions of uniparental disomy greater than 2 Mb are found in the 5q-syndrome and del(5q) myelodysplastic syndrome, although large regions of uniparental disomy (>10 Mb) are only found in the latter group. The recurrent regions of uniparental disomy may indicate the position of novel leukemia-associated genes.
Authors:
Li Wang; Carrie Fidler; Nandita Nadig; Aristoteles Giagounidis; Matteo G Della Porta; Luca Malcovati; Sally Killick; Norbert Gattermann; Carlo Aul; Jacqueline Boultwood; James S Wainscoat
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-27
Journal Detail:
Title:  Haematologica     Volume:  93     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-02     Completed Date:  2008-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  994-1000     Citation Subset:  IM    
Affiliation:
LRF Molecular Haematology Unit, Nuffield Department of Clinical, Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Case-Control Studies
Chromosome Deletion*
Female
Genetic Predisposition to Disease
Genome, Human
Humans
Loss of Heterozygosity*
Male
Middle Aged
Myelodysplastic Syndromes / genetics*
Polymorphism, Single Nucleotide*
Uniparental Disomy / genetics

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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