Evidence that superficial basal cell carcinoma is monoclonal from analysis of the Ptch1 gene locus

Background Superficial basal cell carcinoma (BCC) arises as an apparently multifocal proliferation of tumour nests attached to the epidermis, which is at odds with a monoclonal origin. Computer-assisted reconstruction shows that these nests join in three dimensions, but it remains unknown whether this tumour is monoclonal. An early event in BCC formation, loss of heterozygosity (LOH) at the Patched 1 (Ptch1) locus, can be used as a tool to address whether this tumour is monoclonal. Objectives To determine whether superficial BCC is monoclonal by analysing individually microdissected superficial BCC nests and looking for the same pattern of LOH in each. Methods Six cases of superficial BCC were analysed for LOH at the Ptch1 gene locus using the D9S287 microsatellite marker. Identical allelic patterns were sought in each nest from a given tumour. These patterns were no allelic loss, loss of the shorter allele or loss of the longer allele, each with a respective probability of occurrence, as estimated from published findings. Results All cases were informative. Four cases showed no LOH in each nest and two showed loss of the same allele. If these nests arose independently, then the probability of this result was between 4 x 10(-11) and 2 x 10(-14). The lack of LOH, seen in four cases, could be due to monoclonal expansion of a cell retaining both D9S287 alleles, or due to a polyclonal proliferation. Therefore, a separate analysis excluding these cases was done, giving a probability of between 2.2 x 10(-4) and 1.0 x 10(-7). Conclusions These probabilities were so extreme that it was unlikely that the nests arose independently, thus providing the first molecular evidence that superficial BCC is monoclonal.