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Lookup NU author(s): Professor Julie Irving, Clare Bloodworth, Dr Nicholas Bown, Marian Case, Dr Linda Hogarth, Dr Andrew Hall
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Loss of heterozygosity (LOH) is detectable in many forms of malignancy, including leukemia, using techniques such as microsatellite analysis and comparative genomic hybridization. However, these techniques are laborious and require the use of relatively large amounts of DNA if the whole genome is to be examined. Here we describe the use of oligonucleotide nucroarrays to characterize single nucleotide polymorphisms (SNPs) in lymphoblasts isolated from children with acute lymphoblastic leukemia for the pan-genomic mapping of LOH with a resolution of 100 to 200 kb. Results were compared with DNA obtained during remission and on relapse. Abnormalities were seen in 8 of 10 cases. The two cases with no abnormalities and one case that showed identical changes at relapse and presentation remain in remission I to 9 years following retreatment. The remaining seven patients died following relapse. In four cases, LOH was only detectable at relapse suggesting that progressive LOH may be a cause of disease progression and/or drug resistance. This was supported by detailed analysis of one case in which LOH involving the glucocorticoid receptor was associated with mutation of the remaining allele. The most frequent abnormality detected involved chromosome 9p. In each of the four cases where this was observed LOH included the INK4 locus. In three of the four cases, INK4 loss was only observed at relapse, suggesting that this abnormality may be commonly associated with treatment failure. These observations show that SNP array analysis is a powerful new tool for the analysis of allelic imbalance in leukemic blasts.
Author(s): Irving JAE, Bloodworth LC, Bown NP, Case MC, Hogarth LA, Hall AG
Publication type: Article
Publication status: Published
Journal: Cancer Research
Year: 2005
Volume: 65
Issue: 8
Pages: 3053-3058
ISSN (print): 0008-5472
ISSN (electronic): 1538-7445
URL: http://cancerres.aacrjournals.org/cgi/content/abstract/65/8/3053
PubMed id: 15833833
