Genetic alterations in TP53 in recurrent urothelial cancer: A longitudinalstudy

Purpose: Because bladder cancer has a recurrence rate that can be as high a s 90% at 2 years, we sought to clarify whether these metachronous tumors ar e polyclonal or monoclonal in origin. We have examined the genetic alterati ons of the TP53 gene in a cohort of patients with urothelial cancer who und erwent multiple biopsies at different times and sites because of tumor recu rrence and/or progression. We postulated that if tumor cells at different p oints in the natural history of the disease contain an identical mutation i n the TP53 gene, this pattern could provide evidence for the monoclonality of the recurrent bladder tumors. Experimental Design: Fifty-three biopsy specimens from 13 patients at diffe rent times and sites were selected for this study. Microdissection was used to ensure the purity of tumor cells. DNA extraction, PCR, and direct seque ncing of exons 5 through 8 of the TP53 gene were conducted following protoc ols optimized in our laboratory. Results: We found that specimens from seven patients carried tumor-specific TP53 mutations. The number of lesions in these patients ranged from two to seven, extending from 2 to 4 years. All of the seven patients displayed id entical mutations in the different microdissected tumors. Conclusions: On the basis of these data, it appears that the recurrent blad der tumors originate from the same clone.