Fig. 1.

Models of LOH. Boxes = genes; “X” = inactivating mutation; A, B = alternative alleles of a single nucleotide polymorphism. In the top panels, the black line on the graph represents the overall frequency of LOH observed in tumour samples across the chromosome, while the red bars are the frequency of mutation in a particular gene. Thus, for the classic two-hit model, the frequency of mutation is similar to the frequency of LOH, while in the low frequency model, the frequency of LOH is higher than the mutation rate, because each sample is mutated in a different gene. In the bar graphs below, at left, the red bars represent the frequency of the A allele that is retained in samples with LOH at the locus; thus, the risk locus (*) has a higher proportion of the risk allele (A) retained after LOH compared to a non-risk locus, where the A and B alleles are equally retained. At right, the graphs represents the average reduction in expression of a gene in samples with LOH, compared to samples without LOH; genes in LOH regions show a reduction in expression