© Kamla-Raj 2007 Int J Hum Genet, 7(1): 49-56 (2007) DNA Microarray and Breast Cancer-A Review Ramanathan S. Uma and T. Rajkumar Department of Molecular Oncology, Cancer Institute (W.I.A), Chennai 600 020, Tamil Nadu, India KEYWORDS Gene expression; breast cancer; DNA microarray ABSTRACT Microarray is a powerful tool used widely to characterize tumors and has greatly improved the ability to subclassify tumors according to shared molecular characteristics and clinical behavior. It is a method to measure the expression of a large number of genes in any specimen simultaneously. Researchers at Stanford University were the first to describe and use DNA microarray to study gene expression in various diseases including cancer. Breast cancer is the second most common cancer among Indian women. Multiple factors like age, diet, obesity, parity, age at first childbirth, oral contraceptives, exogenous estrogens, genetics, environment, geographic location influence the development of this heterogeneous disease. Gene expression in these cancers by microarray is fast gaining in popularity in providing better prognostic and predictive information on the disease. This review is an attempt to look at the recent advances in breast cancer research with DNA microarray technology. INTRODUCTION Breast cancer management is a major concern to the clinician due to its extensive heterogeneity. The markers currently associated with the clinical implications include estrogen receptor (ER), progesterone receptor (PR), oncogene her2/neu; others such as cell proliferation marker Ki-67 antigen, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), CD31, Factor VIII etc. are yet to be proven clinical value (Desai et al. 2002). It would help patients if prognostic markers are available which can help identify patients who are likely to fail surgery. Similarly, predictive markers which can help identify a patient who is unlikely to respond to a particular drug/drugs, will be useful in avoiding failures due to lack of efficacy of the drug and avoiding unnecessary morbidity. Molecular biological methods like cytogenetics, comparative genomic hybridization, whole genome allelotyping, single nucleotide polymor- phism studies on candidate genes, differential display, immunohistochemistry among others have shown great promise in addressing the issue at genetic levels. Studying genes at level of transcription (RNA) will give an idea of those that are expressed and analysis of multiple genes simultaneously rather than one at a time will be time saving, less laborious and more predictive. Two methods commonly used now to look at a large number of genes at the mRNA levels are microarray and multiplex quantitative real-time PCR (Rouzier et al. 2005). Apart from gene expression, microarray also finds application in disease diagnosis, drug discovery and toxicological research. WHAT IS A MICROARRAY ? A microarray is an orderly arrangement of known genes attached to a solid support. Each gene on the solid support referred to as spot or probe is usually less than 200μM in diameter. Each spot has a unique sequence different from the others in the array and will hybridize only to its complementary strand. The first arrays with cDNA clones were spotted onto nylon membrane (Desai et al. 2002) and probed with radiolabeled RNA. These should ideally be able to measure gene expression but slide based arrays first adapted by printing cDNA clones onto glass slides that are specially treated with an adherent polylysine or aminosilane have proven to be smaller, convenient and facilitate higher through- put (Jeffrey et al. 2002). There are two strategies for formatting of the slide/chip: - in-situ oligo synthesis or DNA may be directly applied to the surface with nibs or inkjet (Cooper 2001). The entire array can contain anything between 200- 40,000 such spots/genes. The slides or chips, as they are referred to, can be high density chips or low density chips depending on the number of genes spotted on them. Affymetrix Inc.’s GeneChip technology (for Corresponding Author: Dr. T. Rajkumar, Director & Scientific Director, Head, Department of Molecular Oncology, Cancer Institute (W.I.A), Adyar, Chennai 600 020, Tamil Nadu, India Telephone: + 91-44-22350131; +91-44-22350241 Fax: +91-44-24912085 E-mail: cancer_institute_wia@vsnl.com