Some tumors of the bladder are polyclonal in origin

Purpose: Clonality assays can be used to address different questions of neoplasm development. The study of the X chromosome inactivation pattern in female patients provides a useful and most commonly used indirect approach to demonstrate the monoclonal status of a cell population. We used this approach to examine whether recurrent tumors of the bladder supposed to be of monoclonal origin derive from different, independently transformed cells or whether they arise from 1 primary tumor. Materials and Methods: We analyzed 45 archival or fresh frozen bladder tumors from 27 female patients. We assessed the X inactivation status of each tumor by a polymerase chain reaction based method after HpaII digestion. Results: Surprisingly 16 of the 45 tumors revealed a polyclonal pattern, The amount of undigested DNA far exceeded what was explained by contamination with normal cells, as determined on histological sections indicating that these tumors were in fact polyclonal. This polyclonal status was further confirmed by a comprehensive series of controls. Conclusions: Some bladder tumors are polyclonal in origin. Our findings are at variance with earlier observations and possibilities for explanation are proposed.