Figure 1
Strategy used to construct genomic model of bladder cancer. The primary screening with hypervariable DNA markers was performed on paired samples of non-tumor and invasive tumor DNA. Markers showing LOH were selected for secondary screening on all mucosal samples of the same cystectomy. Markers mapping to autosomes 1–22 were tested on five cystectomy specimens. The pattern of LOH on chromosomes 1–22 was used to construct a genome-wide map of bladder cancer development and to identify six chromosomal regions critical for clonal expansion of in situ neoplasia. Finally, the high-resolution mapping was performed on one of the critical chromosomal regions containing a model tumor suppressor, RB1. These studies defined a minimal deleted region associated with clonal expansion of intraurothelial neoplasia around RB1 and permitted the identification of novel target FR genes providing growth advantage for this expansion.
