Background: Despite continuous research efforts in the past decades, there are still cancers where no effective treatment is available, such as advanced kidney cancer or hormone–refractory prostate cancer. A better understanding of the molecular mechanisms of cancer development and progression is the basis for the development of new diagnostic and therapeutic strategies. Current developments in genomics have a dramatic impact on the whole field of research. The sequence of the entire human genome will soon be fully sequenced and provide the ‘book of life’ as a basis for the understanding of human disease. Methods and Results: New technologies have emerged to translate the human genome sequence into gene function and improved diagnostics or treatment modalities. New technologies such as microarrays are not only important for fundamental research, but will also be useful for diagnostic, prognostic or therapeutic purposes in individual patients. DNA microarrays make it possible to analyze the mRNA expression of thousands of genes simultaneously. The resulting comprehensive gene expression surveys lead to the identification of new genes and pathways with importance in cancer development and progression, or as targets for new therapies. The validation and prioritization of genes emerging from genome screening analyses in large series of clinical tumors has become a new bottleneck in research. Therefore, we have recently developed the tissue microarray (TMA) technology to efficiently test the clinical relevance of candidate genes. TMAs are microscope slides containing samples from hundreds of individual tumor specimens. They can be used for large–scale, massively parallel in situ analysis of genetic alterations on a DNA, RNA and protein level using in situ hybridization or immunohistochemistry on hundreds of tumor specimens at a time. Microarray technologies are already increasingly being used in urologic research, and will also have a strong impact on clinical urology. Conclusions: DNA microarrays and TMAs provide a powerful approach to identify large numbers of new candidate genes, and rapidly validate their clinical impact in large series of human tumors. These technologies will soon lead to a better molecular understanding of urologic tumors, and accelerate the identification of new prognostic markers or therapeutic targets.

Keywords:
Microarrays, Genome screening, Tissue chips, Tissue microarray, High–throughput analysis
1.
Collins FS: Shattuck lecture – Medical and societal consequences of the Human Genome Project. N Engl J Med 1999;341:28–37.
2.
Bentley DR: The human genome project – An overview. Med Res Rev 2000;20:189–196.
3.
Smaglik P: Genome leaders told to keep their eyes on the main prize. Nature 2000;404:111.
4.
Cardon LR, Watkins H: Waiting for the working draft from the human genome project. A huge achievement, but not of immediate medical use. BMJ 2000;320:1223–1224.
5.
De Risi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM: Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 1996;14:457–460.
6.
Velculescu VE, Zhang L, Vogelstein B, Kinzler KW: Serial analysis of gene expression. Science 1995;270:484–487.
7.
Lander ES: Array of hope. Nat Genet 1999;21: 3–4.
8.
Lipshutz RJ, Fodor SP, Gingeras TR, Lockhart DJ: High density synthetic oligonucleotide arrays. Nat Genet 1999;21:20–24.
9.
Bowtell DD: Options available – from start to finish – for obtaining expression data by microarray. Nat Genet 1999;21:25–32.
10.
Brown PO, Botstein D: Exploring the new world of the genome with DNA microarrays. Nat Genet 1999;21:33–37.
11.
Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high–throughput molecular profiling of tumor specimens. Nat Med 1998; 4:844–847.
12.
Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM: Expression profiling using cDNA microarrays. Nat Genet 1999;21:10–14.
13.
Bubendorf L, Kolmer M, Kononen J, Koivisto P, Mousses S, Chen Y, Mahlamaki E, Schraml P, Moch H, Willi N, Elkahloun AG, Pretlow TG, Gasser TC, Mihatsch MJ, Sauter G, Kallioniemi OP: Hormone therapy failure in human prostate cancer: Analysis by complementary DNA and tissue microarrays. J Natl Cancer Inst 1999;91:1758–1764.
14.
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibishirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM, et al: Distinct types of diffuse large B–cell lymphoma identified by gene expression profiling. Nature 2000;403:503–511.
15.
Schraml P, Kononen J, Bubendorf L, Moch H, Bissig H, Nocito A, Mihatsch MJ, Kallioniemi OP, Sauter G: Tissue microarrays for gene amplification surveys in many different tumor types. Clin Cancer Res 1999;5:1966–1975.
16.
Bubendorf L, Kononen J, Koivistor P, Schraml P, Moch H, Gasser TC, Willi N, Mihatsch MJ, Sauter G, Kallioniemi OP: Survey of gene amplification during prostate cancer progression by high–throughput fluorescence in situ hybridisation on tissue microarrays. Cancer Res 1999;59:803–806.
17.
Moch H, Schraml P, Bubendorf L, Mirlacher M, Kononen J, Gasser T, Mihatsch MJ, Kallioniemi OP, Sauter G: High–throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma. Am J Pathol 1999;154: 981–986.
18.
Barlund M, Forozan F, Kononen J, Bubendorf L, Chen Y, Bittner ML, Torhorst J, Sauter G, Kallioniemi OP, Kallioniemi A: Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. J Natl Cancer Inst 2000;92:1252–1259.
19.
Mucci NR, Akdas G, Manely S, Rubin MA: Neuroendocrine expression in metastatic prostate cancer: Evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum Pathol 2000;31:406– 414.
20.
Perrone EE, Theoharis C, Mucci NR, Hayasaka S, Taylor JM, Cooney KA, Rubin MA: Tissue microarray assessment of prostate cancer tumor proliferation in African–American and white men. J Natl Cancer Inst 2000;92:937– 939.
21.
Richter J, Wagner U, Kononen J, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knonagel H, Rist M, Wilber K, Anabitarte M, Hering F, Hardmeier T, Schonenberger A, Flury R, Jager P, Fehr JL, Schraml P, Moch H, Mihatsch MJ, Gasser T, Kallioniemi OP, Sauter G: High–throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. Am J Pathol 2000;157:787–794.
22.
Bowen C, Bubendorf L, Voeller HJ, Slack R, Willi N, Sauter G, Gasser TC, Koivisto P, Lack EE, Kononen J, Kallioniemi OP, Gelmann EP: Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression. Cancer Res 2000;60:6111–6115.
23.
Cohen P, Peehl DM, Lamson G, Rosenfeld RG: Insulin–like growth factors (IGFs), IGF receptors, and IGF–binding proteins in primary cultures of prostate epithelial cells. J Clin Endocrinol Metab 1991;73:401–407.
24.
Clemmons DR: Role of insulin–like growth factor binding proteins in controlling IGF actions. Mol Cell Endocrinol 1998;140:19–24.
25.
Elek J, Park KH, Narayanan R: Microarray–based expression profiling in prostate tumors. In Vivo 2000;14:173–182.
26.
Carlisle AJ, Prabhu VV, Elkahloun A, Hudson J, Trent JM, Linehan WM, Williams ED, Emmert–Buck MR, Liotta LA, Munson PJ, Krizman DB: Development of a prostate cDNA microarray and statistical gene expression analysis package. Mol Carcinog 2000;28:12– 22.
27.
Howell SB: DNA Microarrays for analysis of gene expression. Mol Urol 1999;3:295–300.
28.
Amler LC, Agus DB, LeDuc C, Sapinoso ML, Fox WD, Kern S, Lee D, Wang V, Leysens M, Higgins B, Martin J, Gerald W, Dracopoli N, Cordon–Cardo C, Scher HI, Hamptom GM: Dysregulated expression of androgen–responsive and nonresponsive genes in the androgen–independent prostate cancer xenograft model CWR22–R1. Cancer Res 2000;60:6134–6141.
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.