Karyotypic characterization of urinary bladder transitional cell carcinomas

Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-ban ding of the chromosomes. Clonal chromosome abnormalities were detected in 2 7 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC path ogenesis. There was no clonal heterogeneity within individual tumors, conso nant with the view that TCCs are monoclonal in origin. The most striking fi nding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rea rrangement in 8. The changes in chromosome 9 always led to loss of material ; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, u nbalanced structural rearrangements were seen, of which del(1)(p11), add(3) (q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del (14)(q24), and i(17)(q10) are described here for the first time. The karyot ypic imbalances were dominated by losses of the entire or parts of chromoso me arms Ip, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosome s 9, 14, 16, i 8, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric break points preferentially involved in structural rearrangements were 1q12, 2q11 , 5q11,8q24, 9p13, 9q13, 9q22, 11p11,and 13p10. Rearrangements of 17p and t he formation of an i(5)(p10) were associated with more aggressive tumor phe notypes. There was also a general correlation between the tumors' grade/sta ge and karyotypic complexity, indicating that progressive accumulation of a cquired genetic alterations is the driving force behind multistep bladder T CC carcinogenesis. (C) 2000 Wiley-Liss, Inc.