Loss of heterozygosity (LOH), either with or without accompanying copy-number 
loss, is a cardinal feature of cancer genomes that is tightly linked to cancer 
development. However, detection of LOH is frequently hampered by the presence of 
normal cell components within tumor specimens and the limitation in availability 
of constitutive DNA. Here, we describe a simple but highly sensitive method for 
genomewide detection of allelic composition, based on the Affymetrix 
single-nucleotide-polymorphism genotyping microarray platform, without 
dependence on the availability of constitutive DNA. By sensing subtle 
distortions in allele-specific signals caused by allelic imbalance with the use 
of anonymous controls, sensitive detection of LOH is enabled with accurate 
determination of allele-specific copy numbers, even in the presence of up to 
70%-80% normal cell contamination. The performance of the new algorithm, called 
"AsCNAR" (allele-specific copy-number analysis using anonymous references), was 
demonstrated by detecting the copy-number neutral LOH, or uniparental disomy 
(UPD), in a large number of acute leukemia samples. We next applied this 
technique to detection of UPD involving the 9p arm in myeloproliferative 
disorders (MPDs), which is tightly associated with a homozygous JAK2 mutation. 
It revealed an unexpectedly high frequency of 9p UPD that otherwise would have 
been undetected and also disclosed the existence of multiple subpopulations 
having distinct 9p UPD within the same MPD specimen. In conclusion, AsCNAR 
should substantially improve our ability to dissect the complexity of cancer 
genomes and should contribute to our understanding of the genetic basis of human 
cancers.