Coexistence of copy number changes of different genes (INK4A, erbB-1, erbB-2, CMYC, CCND1 and ZNF217) in urothelial tumors.

The aim of this study was to establish the frequency of combinatorial and separate copy number changes of INK4A (9p21), erbB-1 (7p11), erbB-2 (17q17-21), CMYC (8q24), CCND1 (11q13) and ZNF217 (20q13) in urothelial tumors; a tissue microarray of 159 urothelial bladder tumors was analyzed by fluorescence in situ hybridization. A total of 38 invasive tumors were successfully analyzed for all 6 loci. Normal gene copy numbers of all loci were established in 13 tumors (34.2%). In 25 tumors (65.8%), at least one aberration was found. Single abnormalities were detected in 16 tumors (64%), while double or higher abnormalities were found in 9 tumors (39%). The most frequent genetic change was deletion of INK4A (60% of aberrant tumors), followed by increased copy number changes of ZNF217 (36%), CCND1 (28%), CMYC (12%) and erbB-1 (4%). It was significantly more frequent in pT1 than in pT2-4 tumors and was predominantly found separately, while oncogene copy number increases were usually combined with another aberration and were not associated with the tumor stage. We concluded that INK4A loss is usually found as a single aberration in bladder cancer, which is more frequent in pT1 than in pT2-4 tumors. Overrepresentations of putative oncogenes are present in these two groups with similar frequency and are rarely found as single abnormality.