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Genetic Alterations in TP53 in Recurrent Urothelial Cancer

A Longitudinal Study

Departments of Urology [G. D., H. H.] and Pathology [Z-P. R., C. C-C., V. R.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Purpose: Because bladder cancer has a recurrence rate that can be as high as 90% at 2 years, we sought to clarify whether these metachronous tumors are polyclonal or monoclonal in origin. We have examined the genetic alterations of the TP53 gene in a cohort of patients with urothelial cancer who underwent multiple biopsies at different times and sites because of tumor recurrence and/or progression. We postulated that if tumor cells at different points in the natural history of the disease contain an identical mutation in 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 different times and sites were selected for this study. Microdissection was used to ensure the purity of tumor cells. DNA extraction, PCR, and direct sequencing of exons 5 through 8 of the TP53 gene were conducted following protocols 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 identical mutations in the different microdissected tumors.

Conclusions: On the basis of these data, it appears that the recurrent bladder tumors originate from the same clone.

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