IBCN 2020: Recurring Urothelial Carcinomas Are Clonal But Incompatible with a Direct Relationship

(UroToday.com) Various postulates including field cancerization, seeding, and intraepithelial migration have been proposed to explain the genetic relationship between the primary and recurrent bladder tumors and to identify their origins. Researchers from Lund University, Sweden, performed this study to investigate the genetic relationships in synchronous and metachronous bladder tumors.

Biopsied specimens of primary and recurrent urothelial tumors were analyzed. In total, 49 tumors from 18 patients and their 18 matched normal samples obtained from peripheral blood were collected and genomically profiled. Based on mutational and copy number data, the investigators inferred that recurring tumors from the same patient may be clonal, with complex genomic alterations being stable for several years and appearing as identical aberrations in recurring metachronous tumors. However, they also noted gross genomic chromosomal aberrations that may be present subsequently lost in a recurrent tumor, indicating private changes. By analyses of incompatible changes i.e., genomic alterations that cannot be reversed, they demonstrated that nearly all synchronous and metachronous tumors may show such changes.

As recurrent tumors share both genomic alterations and driver gene mutations, these are likely present in the urothelium at a time when no overt tumor is present. The presence of similar mutational and copy number profiles combined with incompatible events suggests that primary and recurrent tumors have a shared ancestry but do not originate from each other. This supports a model that includes a growing and evolving field of urothelial cells that occasionally, and locally, produce bursts of cellular growth leading to overt tumors (Figure).

Figure: Proposed schema of synchronous and metachronous bladder tumor evolution.

Presented by: Nour-al-dain Marzouka, Ph.D., Department of Clinical Sciences, Lund University, Sweden

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