Patterns of chromosomal imbalances in advanced urinary bladder cancer detected by comparative genomic hybridization

Abstract

To identify genetic changes linked to bladder cancer progression we analyzed 90 invasive transitional cell carcinomas (37 pT1 and 53 pT2-4) by comparative genomic hybridization. The most frequent alterations included 1q+ (37%), 5p+ (24%), 6q- (19%), 8p-(29%), 8q+ (37%), 9p- (31%), 9q- (23%), 11p-(24%), 11q- (22%), 17q+ (29%), and 20q+ (28%). Interestingly, there were three groups of alterations that frequently occurred together (9p- and 11q13+/ 20q+ and 11q13+ or 17q+/1q+ and 3p+ or 11q-). These loci might carry genes that interact with each other in specific molecular pathways. There were remarkable genetic similarities between minimally and deeply invasive tumors of different histological grades, including a similar number of aberrations per tumor and an equal frequency of most individual alterations. However, deletions of 5q, 6q, and 15q and gains of 5p, 7p, and Xq were significantly more frequent in pT2-4 than in pT1 carcinomas. These loci may harbor genes that are important for bladder cancer progression.

Figure 1.

Summary of all relative DNA sequence copy number changes detected by CGH in 37 papillary pT1 (A), 24 papillary pT2–4 (B), and 29 solid pT2–4 carcinomas (C). The vertical lines on the right side of the chromosome idiograms indicate gains, those on the left losses of the corresponding chromosomal regions. Amplifications are indicated as solid bars. *1p, 16p, 19, and 22 were not analyzed.

Figure 2.

Relationship between individual alterations. Tumors with 20q gains had an increased likelihood to have also 11q13 gains or 17q gains. Carcinomas with 1q gains had frequent 3p gains and 11q deletions.

Figure 3.

A putative model of bladder cancer development and progression based on molecular cytogenetic findings. For explanations, see text.