Study of loss of heterozygosity (LOH) is widely used to identify chromosomal locations of putative tumor suppressor genes. In this type of analysis, DNA extracted from tumor tissue is compared with constitutive DNA from the same patient by the use of polymorphic DNA markers (1 ). This approach has two intrinsic limitations. First, tumor specimens with a high fraction of nonneoplastic cells have to be excluded from this analysis because LOH in tumor cells may be undetectable, because of the low concentration of tumor DNA. This may lead to a selection bias, which affects the representativity of the results. A second limitation is that the analysis of DNA extracted from homogenized tumor samples may obscure the presence of intratumor genetic heterogeneity.
