Nonparametric estimation of LOH using Affymetrix SNP genotyping arrays for unpaired samples.

Studies of loss of heterozygosity (LOH) play an important role in cancer research. In this paper, we developed a two-step procedure to examine LOH by comparing unpaired tumour and normal samples. In the first step we determined which chromosomes significantly differ between the two sets of samples by using nonparametric procedures. We then used the biplot data visualisation technique and homozygosity intensity estimates to determine the regions of these chromosomes that required further examination. We illustrated our method by examining 22 autosomes in samples of 95 normal controls and 14 acute lymphoblastic leukaemia patients. The genomewide scan of LOH with the Affymetrix Human Mapping 100K Set successfully identified the important tumour suppressor gene, CDKN2A, whose deletion was validated by quantitative polymerase chain reaction in multiple patients of this study.