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KL Emerging mechanisms of tumor initiation and progression: lessons from the bladder cancer model. Emerging mechanisms of tumor initiation and progression: lessons from the bladder cancer model. Bladder cancer has served as one of the most important sources of information about the events that underlie the development of human solid malignancies.
More recently, whole organ mapping combined with genomic platforms have identified a novel class of candidate tumor suppressors forerunner genes that localize near more familiar tumor suppressors but are disrupted at an earlier stage of cancer development. These studies suggested three steps for the involvement of the model tumor suppressor locus, RB1, in tumor development.
In the first step, one allele of forerunner FR gene and RB1 is inactivated by deletions. In the second step, homozygous inactivation of the FR genes is accomplished by hypermethylation or mutations.
The inactivation of FR genes is associated with the initial clonal expansion of preneoplastic urothelial cells. In the third step, the contiguous tumor suppressor, RB1, is inactivated by a mutation, which is associated with clonal evolution into carcinoma in situ progressing to invasive cancer. Pathology as a medical specialty has been around for about a century and a half, even though the interest in understanding disease, the focus of pathology as an academic discipline, has inspired physicians since the dawn of mankind.
