Critical Reviews in Oncology/Hematology 54 (2005) 95–105 Gene expression arrays in cancer research: methods and applications Ricardo R. Brentani a,b,* , Dirce Maria Carraro a , Sergio Verjovski-Almeida c , Eduardo M. Reis c , E. Jord˜ ao Neves d , Sandro J. de Souza a , Alex F. Carvalho a , Helena Brentani b , Luiz F.L. Reis a,b a LudwigInstituteforCancerResearch,S˜ aoPaulo,Brazil b HospitaldoCˆ ancerA.C.Camargo,S˜ aoPaulo,Brazil c InstitutodeQu´ ımica,UniversidadedeS˜ aoPaulo,S˜ aoPaulo,Brazil d InstitutodeMatem´ aticaeEstat´ ıstica,andBIOINFO,UniversidadedeS˜ aoPaulo,S˜ aoPaulo,Brazil Accepted 14 December 2004 Contents 1. Introduction ......................................................................................................................... 96 2. How to build a chip? ................................................................................................................. 96 3. What kind of questions for what kind of chip? .......................................................................................... 99 4. The Universal chip ................................................................................................................... 99 5. Designer chips ....................................................................................................................... 99 5.1. The Intron chip ................................................................................................................ 99 5.2. The tumor-associated splice chip ............................................................................................... 100 5.3. Pathway-specific arrays ....................................................................................................... 100 6. What is the best source for RNA? ..................................................................................................... 101 7. Bioinformatics ...................................................................................................................... 101 8. Data analysis ....................................................................................................................... 102 8.1. Clustering samples and genes .................................................................................................. 102 8.2. Molecular classifiers in cancer ................................................................................................. 103 Reviewers .......................................................................................................................... 103 Acknowledgments .................................................................................................................. 104 References ......................................................................................................................... 104 Biography .......................................................................................................................... 105 Abstract During the last 5 years, the number of papers describing data obtained by microarray technology increased exponentially with about 3000 papers in 2003. Undoubtedly, cancer is by far the disease that received most of the attention as far as the amount of data generated. As array technology is rather new and highly dependent on bioinformatics, mathematics and statistics, a clear understanding of the knowledge and information derived from array-based experiments is not widely appreciated. We shall review herein some of the issues related to the construction of DNA arrays, quantities and heterogeneity of probes and targets, the consequences of the physical characteristics of the probes, data extraction and data analysis as well as the applications of array technology. Our goal is to bring to the general audience, some of the basics of array technology and its possible application in oncology. By discussing some of the basic aspects of the methodology, we hope to stimulate criticism concerning the conclusions proposed by authors, especially in * Corresponding author. Present address: Rua Prof Antonio Prudente 109, 4th floor, S˜ ao Paulo 01509-010, Brazil. Tel.: 55 11 33883202; fax: +55 11 32077001. E-mailaddress: rbrentani@ludwig.org.br (R.R. Brentani). 1040-8428/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2004.12.006