This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Cairns, P. Articles by Sidransky, D. Search for Related Content PubMed PubMed Citation Articles by Cairns, P. Articles by Sidransky, D.

Homozygous Deletions of 9p21 in Primary Human Bladder Tumors Detected by Comparative Multiplex Polymerase Chain Reaction¹

Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Deletion mapping studies of primary bladder tumors have identified nonoverlapping areas of loss on each arm of chromosome 9, indicating that two distinct tumor suppressor loci are located on this chromosome. The deleted region on the p arm overlaps an area of 9p previously reported to be lost in a variety of neoplasms. Detailed loss of heterozygosity analysis of 9p in 112 primary bladder tumors using 12 microsatellite markers identified a minimal area of loss around the -interferon locus at 9p21–22. Frequent homozygous deletions of the -interferon locus were then identified in these tumors by a novel, comparative, multiplex polymerase chain reaction assay and were subsequently confirmed by Southern analysis. Based on these deletions, a putative tumor suppressor gene locus involved in bladder tumorigenesis was localized to a 10 cM region (flanked by D9S162 and D9S171), previously implicated in the progression of many neoplasms. Application of the multiplex polymerase chain reaction-based assay will allow rapid identification of homozygous deletions in many neoplasms and thus aid in mapping studies of critical suppressor genes.

¹ Supported by a collaborative research agreement with Oncor, Inc. of Gaithersburg, MD.

² To whom requests for reprints should be addressed, at Department of Otolaryngology, Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University, School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196.

Received 1/ 6/94. Accepted 2/ 4/94.

This article has been cited by other articles:

				J. Gu, Y. Horikawa, M. Chen, C. P. Dinney, and X. Wu Benzo(a)pyrene Diol Epoxide-Induced Chromosome 9p21 Aberrations Are Associated with Increased Risk of Bladder Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2008; 17(9): 2445 - 2450. [Abstract] [Full Text] [PDF]

				G. P. Flake, M. P. Rivera, W. K. Funkhouser, S. J. Maygarden, K. L. Meadows, E. H. Long, P. S. Stockton, T. C. Jones, H. W. Yim, R. J.C. Slebos, et al. Detection of Pre-Invasive Lung Cancer: Technical Aspects of the LIFE Project Toxicol Pathol, January 1, 2007; 35(1): 65 - 74. [Abstract] [Full Text] [PDF]

				M. A. Knowles Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis, March 1, 2006; 27(3): 361 - 373. [Abstract] [Full Text] [PDF]

				L. Cheng, T. D. Jones, R. P. McCarthy, J. N. Eble, M. Wang, G. T. MacLennan, A. Lopez-Beltran, X. J. Yang, M. O. Koch, S. Zhang, et al. Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma Am. J. Pathol., May 1, 2005; 166(5): 1533 - 1539. [Abstract] [Full Text] [PDF]

				J. S. Aveyard and M. A. Knowles Measurement of Relative Copy Number of CDKN2A/ARF and CDKN2B in Bladder Cancer by Real-Time Quantitative PCR and Multiplex Ligation-Dependent Probe Amplification J. Mol. Diagn., November 1, 2004; 6(4): 356 - 365. [Abstract] [Full Text] [PDF]

				P. Berggren, R. Kumar, S. Sakano, L. Hemminki, T. Wada, G. Steineck, J. Adolfsson, P. Larsson, U. Norming, H. Wijkstrom, et al. Detecting Homozygous Deletions in the CDKN2A(p16INK4a)/ARF(p14ARF) Gene in Urinary Bladder Cancer Using Real-Time Quantitative PCR Clin. Cancer Res., January 1, 2003; 9(1): 235 - 242. [Abstract] [Full Text] [PDF]

				W. M. Stadler, G. Steinberg, X. Yang, F. Hagos, C. Turner, and O. I. Olopade Alterations of the 9p21 and 9q33 Chromosomal Bands in Clinical Bladder Cancer Specimens by Fluorescence in Situ Hybridization Clin. Cancer Res., June 1, 2001; 7(6): 1676 - 1682. [Abstract] [Full Text] [PDF]

				P. M. Pollock, J. Welch, and N. K. Hayward Evidence for Three Tumor Suppressor Loci on Chromosome 9p Involved in Melanoma Development Cancer Res., February 1, 2001; 61(3): 1154 - 1161. [Abstract] [Full Text]

				P. Schraml, K. Struckmann, R. Bednar, W. Fu, T. Gasser, K. Wilber, J. Kononen, G. Sauter, M. J. Mihatsch, and H. Moch CDKN2A Mutation Analysis, Protein Expression, and Deletion Mapping of Chromosome 9p in Conventional Clear-Cell Renal Carcinomas : Evidence for a Second Tumor Suppressor Gene Proximal to CDKN2A Am. J. Pathol., February 1, 2001; 158(2): 593 - 601. [Abstract] [Full Text] [PDF]

				C.-T. Lee, J. Y. Seol, K.-H. Park, C.-G. Yoo, Y. W. Kim, C. Ahn, Y.-W. Song, S. K. Han, J. S. Han, S. Kim, et al. Differential Effects of Adenovirus-p16 on Bladder Cancer Cell Lines Can Be Overcome by the Addition of Butyrate Clin. Cancer Res., January 1, 2001; 7(1): 210 - 214. [Abstract] [Full Text]

				H.-X. An, A. Claas, L. Savelyeva, S. Seitz, P. Schlag, S. Scherneck, and M. Schwab Two Regions of Deletion in 9p23-24 in Sporadic Breast Cancer Cancer Res., August 1, 1999; 59(16): 3941 - 3943. [Abstract] [Full Text] [PDF]

				M. Mateo, M. Mollejo, R. Villuendas, P. Algara, M. Sanchez-Beato, P. Martinez, and M. A. Piris 7q31-32 Allelic Loss Is a Frequent Finding in Splenic Marginal Zone Lymphoma Am. J. Pathol., May 1, 1999; 154(5): 1583 - 1589. [Abstract] [Full Text] [PDF]

				M. Velickovic, B. Delahunt, and S. K. G. Grebe Loss of Heterozygosity at 3p14.2 in Clear Cell Renal Cell Carcinoma Is an Early Event and Is Highly Localized to the FHIT Gene Locus Cancer Res., March 1, 1999; 59(6): 1323 - 1326. [Abstract] [Full Text] [PDF]

				K. S.J. Elenitoba-Johnson, R. D. Gascoyne, M. S. Lim, M. Chhanabai, E. S. Jaffe, and M. Raffeld Homozygous Deletions at Chromosome 9p21 Involving p16 and p15 Are Associated With Histologic Progression in Follicle Center Lymphoma Blood, June 15, 1998; 91(12): 4677 - 4685. [Abstract] [Full Text] [PDF]

				P Cairns, L Mao, A Merlo, D. Lee, D Schwab, Y Eby, K Tokino, P van der Riet, J. Blaugrund, and D Sidransky Rates of p16 (MTS1) mutations in primary tumors with 9p loss Science, July 15, 1994; 265(5170): 415 - 417. [PDF]

				A. Kamb, Q. Liu, K. Harshman, S. Tavtigian, C. Cordon-Cardo, and M. H. Skolnick Response Science, July 15, 1994; 265(5170): 416 - 417. [PDF]

				R. H. Hruban, P. van der Riet, Y. S. Erozan, and D. Sidransky Molecular Biology and the Early Detection of Carcinoma of the Bladder -- The Case of Hubert H. Humphrey N. Engl. J. Med., May 5, 1994; 330(18): 1276 - 1278. [Full Text]

				M. Hatakeyama, R.A. Herrera, T. Makela, S.F. Dowdy, T. Jacks, and R.A. Weinberg The Cancer Cell and the Cell Cycle Clock Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 1 - 10. [Abstract] [PDF]

				A. Kamb Role of a Cell Cycle Regulator in Hereditary and Sporadic Cancer Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 39 - 47. [Abstract] [PDF]

				A. Okamoto, D.J. Demetrick, E.A. Spillare, K. Hagiwara, S.P. Hussain, W.P. Bennett, K. Forrester, B. Gerwin, M.S. Greenblatt, M. Serrano, et al. p16 INK4 Mutations and Altered Expression in Human Tumors and Cell Lines Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 49 - 57. [Abstract] [PDF]