Highly Sensitive Method for Genomewide Detection of Allelic Composition in Nonpaired, Primary Tumor Specimens by Use of Affymetrix Single-Nucleotide–Polymorphism Genotyping Microarrays

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