GENETIC ALTERATIONS IN PRIMARY BLADDER CANCERS AND THEIR METASTASES

Bladder cancer progression is thought to be associated with sequential genetic events. To search for the specific genetic changes associated with the metastatic process, comparative genomic hybridization was pe rformed on 22 primary tumors and 24 metastases (10 distant and 14 noda l metastases) from 17 patients with stage pT2-4 bladder cancer. There was a striking similarity between the genetic alterations present in t he primary and metastatic tumor samples from the same patient. The mea n number of genetic changes/tumor was 12.2 for primary tumors and 11.7 for metastases, There was a strong concordance in the specific aberra tions present in each patient's primary and metastatic lesions (mean, 75%). Concordance was also high among multiple sites from an individua l primary tumor (mean, 96%) and multiple metastases from the same pati ent (mean, 75%). There were no specific genetic changes overrepresente d in the metastases compared with their primary tumors, Genetic altera tions present in more than 40% of tumors included gains on 6p, 8q, 10q , and 17q and losses involving 8p, 10q, and Y, Two regions of high-lev el amplification were common: (a) 10q22.1-q23.1 (32.6%); and (b) 17q11 -21.3 (23.9%; the locus of erbB-2), A summary statistic was developed to quantitate the degree of clonal relationships between biopsies from the same patient. These data support a model in which minimal clonal evolution occurs in the metastatic tumor cell population after the met astatic event. When comparing primary cancers from patients with and w ithout metastases, however, several unique genetic changes were identi fied in those cancers with metastases, suggesting that these loci may harbor genes important to the metastatic process.