This “second hit” hypothesis was initially proposed by Knudson based on his observations of the incidence of familial retinoblastoma [4] and has been widely accepted as a mechanism for the complete inactivation of tumour suppressor genes, both in a germline context and the sporadic cancer context where the first hit is a somatic event, such as mutation of TP53. As a consequence, mapping of common regions of minimal LOH has historically been a popular strategy to pursue the identification of novel TSGs without the need for segregation data from large cancer families. This evidence concerns the gene TP53 and cancer.