This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Primdahl, H. Articles by Ørntoft, T. F. Search for Related Content PubMed PubMed Citation Articles by Primdahl, H. Articles by Ørntoft, T. F.

Allelic Deletions of Cell Growth Regulators during Progression of Bladder Cancer¹

Molecular Diagnostic Laboratory, Departments of Clinical Biochemistry [H. P., M. C., T. F. Ø.] and Urology [H. W.], Aarhus University Hospital, 8200 Aarhus N, and Department of Oncology, Aarhus University Hospital, 8000 Aarhus C [H. v. d. M.], Denmark

Cell growth regulators include proteins of the p53 pathway encoded by the genes CDKN2A (p16, p14arf), MDM2, TP53, and CDKN1A (p21) as well as proteins encoded by genes like RB1, E2F, and MYCL. In the present study we investigated allelic deletions of all these genes in each recurrent bladder tumor from well-defined clinical material with more than 3 years of follow-up. We followed three groups (22 or 23 patients/group) of patients with: (a) recurrent noninvasive tumors (Ta); (b) primary muscle-invasive tumors (T2–T4); and (c) progressing tumors (Ta/T1 T2/T4). We found a significant difference in the numbers of gene loci hit by deletions in muscle-invasive versus noninvasive tumors (P = 0.0000002), with the genes most often hit by deletions in muscle-invasive tumors being TP53, RB1, and MYCL. A number of novel findings were made. Losses of MYCL and RB1 alleles were more pronounced in patients having concomitant field disease because 11 of 14 informative cases showed losses compared with 3 of 8 cases without field disease. A more pronounced deletion of TP53 (P = 0.002) and RB1 (P = 0.02) was found in the progressing tumor group compared with the recurrent noninvasive group, and, finally, the combined loss of TP53 and RB1 was present only in the progressing tumor or muscle-invasive groups. Deletion of two or more loci in TP53, MYCL, RB1, and CDKN2A was found in 10 patients in the progressing tumor group and in only 1 patient in the recurrent noninvasive group (P = 0.004). The data demonstrate that a characteristic difference between recurrent noninvasive and recurrent progressing bladder tumors is loss of cell cycle-regulatory genes in the latter group.

This article has been cited by other articles:

				S. Hernandez, E. Lopez-Knowles, J. Lloreta, M. Kogevinas, R. Jaramillo, A. Amoros, A. Tardon, R. Garcia-Closas, C. Serra, A. Carrato, et al. FGFR3 and Tp53 Mutations in T1G3 Transitional Bladder Carcinomas: Independent Distribution and Lack of Association with Prognosis Clin. Cancer Res., August 1, 2005; 11(15): 5444 - 5450. [Abstract] [Full Text] [PDF]

				J. N. Davis, M. T. McCabe, S. W. Hayward, J. M. Park, and M. L. Day Disruption of Rb/E2F Pathway Results in Increased Cyclooxygenase-2 Expression and Activity in Prostate Epithelial Cells Cancer Res., May 1, 2005; 65(9): 3633 - 3642. [Abstract] [Full Text] [PDF]

				B. W. G. van Rhijn, T. H. van der Kwast, A. N. Vis, W. J. Kirkels, E. R. Boeve, A. C. Jobsis, and E. C. Zwarthoff FGFR3 and P53 Characterize Alternative Genetic Pathways in the Pathogenesis of Urothelial Cell Carcinoma Cancer Res., March 15, 2004; 64(6): 1911 - 1914. [Abstract] [Full Text] [PDF]

				B. W. G. van Rhijn, I. Lurkin, D. K. Chopin, W. J. Kirkels, J.-P. Thiery, T. H. van der Kwast, F. Radvanyi, and E. C. Zwarthoff Combined Microsatellite and FGFR3 Mutation Analysis Enables a Highly Sensitive Detection of Urothelial Cell Carcinoma in Voided Urine Clin. Cancer Res., January 1, 2003; 9(1): 257 - 263. [Abstract] [Full Text] [PDF]

				H. Primdahl, F. P. Wikman, H. von der Maase, X.-g. Zhou, H. Wolf, and T. F. Orntoft Allelic Imbalances in Human Bladder Cancer: Genome-Wide Detection With High-Density Single-Nucleotide Polymorphism Arrays J Natl Cancer Inst, February 6, 2002; 94(3): 216 - 223. [Abstract] [Full Text] [PDF]

				S. H. Olesen, T. Thykjaer, and T. F. Orntoft Mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in human bladder cancer, screening for mutations and loss of heterozygosity Carcinogenesis, May 1, 2001; 22(5): 813 - 815. [Abstract] [Full Text] [PDF]