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Chromosomal Imbalances Are Associated with a High Risk of Progression in Early Invasive (pT₁) Urinary Bladder Cancer¹

Institute of Pathology [J. R., U. W., P. S., H. M., M. J. M., G. S.] and Urologic Clinics [T. C. G.], University of Basel, 4003 Basel, Switzerland; Institute for Pathology [R. M.] and Urologic Clinics [G. A.], City Hospital Triemli Zürich, 8063 Zürich, Switzerland; Urologic Clinics, Limmattal Hospital Schlieren, 8952 Schlieren, Switzerland [H. K.]

Many cytogenetic alterations are known to occur in urinary bladder cancer, but the significance of most of them is poorly understood. To define these chromosomal regions where clinically relevant genes may be located, a series of 54 pT₁ urinary bladder carcinomas with clinical follow-up information (median, 52 months; range, 5–167 months) were examined by comparative genomic hybridization. The most frequent alterations included DNA sequence copy number gains at 1q22-24 (33%), 20q11.2-ter (33%), 8q22 and 17q21 (28% each), and 6p22 (15%) as well as deletions at Y (37%), 9p (31%), 9q22-33 and 11p14-ter (28% each), 11q23 (26%), 8p (24%), 13q31 (19%), 2q35-ter (17%), and 2q22-33 (11%). Whereas the histological grade was unrelated to prognosis (P = 0.9752), the risk of tumor progression was significantly associated with the number of deletions per tumor (P = 0.0014). Individual cytogenetic alterations that were linked to subsequent tumor progression included gains of 3p22-24 (P = 0.0112) and 5p (P = 0.0003) as well as losses of 4p11-15 (P = 0.0052), 5q15-23 (P = 0.0410), 6q22-23 (P = 0.0090), 10q24-26 (P = 0.0232), and 18q12-23 (P = 0.0005). Genes with a role for bladder cancer progression may be located at these regions.

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