SNP array technology permits the simultaneous analysis of copy number and allelotype data. This approach has revealed the somatic acquisition of uniparental disomy (UPD) in approximately 20% of acute myeloid leukemias (AMLs) (

Raghavan et al.
Cancer Res
2005
;
65
:
375
–378
). UPD, which mostly appears to be the consequence of mitotic recombination, cannot be detected by conventional analysis. We have conducted a pilot investigation of samples from the UK MRC AML 10 trial in order to confirm these findings in a larger data set from a large clinical trial. The Affymetrix 10K GeneChip Mapping Array was used to type DNA from 100 AML blast samples of which 87 produced arrays with call rates in excess of 90%. Analysis was performed using the genome orientated laboratory file (GOLF) system, an in-house software package designed to interpret SNP array data. Control germline DNA was not available for each AML and GOLF was used to create a control copy number experiment from the mean of 52 array data sets from normal tissue (blood and remission marrow). The copy number ratio was calculated for each SNP for each sample. In 44 samples the karyotype concurred with the SNP array results (excluding balanced translocations which cannot be detected by SNP array). In the other samples, 54 abnormalities were detected that were not seen in the karyotype (6 samples had no karyotype information). Nine were amplifications, 12 were deletions and 31 were UPDs (35%). Of the UPDs, 12 were either whole chromosome or extended to the most telomeric SNP, with the others therefore being interstitial changes. The mean size of an interstitial LOH was 13.3 Mb, with the smallest detected being 3.2 Mb. Recurrent chromosomal abnormalities not detected by giemsa banding are listed in table 1. Twenty samples that were regarded as normal karyotype by gene banding had abnormalities by SNP array. In three examples numerical karyotypic abnormalities were not seen on SNP array analysis (add4q, −8 and a hypodiploid AML). This may be because a minority clone of the AML cells had this karyotype. UPD is known to be associated with homozygous mutations in AML (Fitzgibbon et al. Cancer Res 2005; in press). In this series, two patients had UPD13, both with biallelic FLT3 internal tandem duplication mutations. However, this study has identified several new areas to look for potential homozygous mutations. Given that in this study germ-line comparison has not been made one should not rule out the possibility of some of the smaller abnormalities being copy number polymorphisms (
Bailey et al.
Science
2005
;
297
;
1003
–1007
). However, consanguinity can probably be ruled out given the lack of widespread homozygosity. This study confirms the frequency of UPD and illustrates the potential of SNP arrays for highlighting novel genetic events in AML.

Table 1:

Recurrent chromosomal abnormalities not detected by gene banding

Previously Undetected AbnormalityNumber
UPD1p 2 
Amplified 1p 2 
UPD2p 2 
Del7q 3 
UPD8p 2 
UPD11p 2 
UPD11q 3 
Amplified 12 3 
Amplified 13 2 
UPD16p 4 
UPD16q 2 
Del20q 2 
Previously Undetected AbnormalityNumber
UPD1p 2 
Amplified 1p 2 
UPD2p 2 
Del7q 3 
UPD8p 2 
UPD11p 2 
UPD11q 3 
Amplified 12 3 
Amplified 13 2 
UPD16p 4 
UPD16q 2 
Del20q 2 
View Large

Topics:
karyotype determination procedure, leukemia, myelocytic, acute, single nucleotide polymorphism, uniparental disomy, cancer, dna, consanguinity, disease remission, giemsa stain, magnetic resonance cholangiography

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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