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Target Discovery and Validation Reviews and Protocols

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5<br />

Molecular Classification of Breast Tumors<br />

Toward Improved Diagnostics <strong>and</strong> Treatments<br />

Therese Sørlie<br />

Summary<br />

Recent advances in gene expression profiling <strong>and</strong> other “omics” technologies have revolutionized<br />

cancer research <strong>and</strong> hold the potential of also revolutionizing clinical practice. These<br />

high-throughout approaches have radically changed our ability to study cells <strong>and</strong> tissues in a more<br />

comprehensive way. Combined with advanced bioinformatics <strong>and</strong> the possibility to simulate biological<br />

processes in computers, this field of “systems biology” allows us to study the organism as<br />

a whole entity. This chapter describes the molecular classification <strong>and</strong> characterization of breast<br />

tumors into distinct subtypes by using DNA microarrays <strong>and</strong> discusses the statistical relationships<br />

of the subgroups with clinical features of the disease.<br />

Key Words: Breast cancer, DNA microarrays, gene expression patterns; prediction; prognosis.<br />

1. Introduction<br />

Cancer diseases result from the accumulation of mutations, chromosomal<br />

instabilities <strong>and</strong> epigenetic changes that together facilitate an increased rate of<br />

cellular evolution <strong>and</strong> damage that progressively impairs the cell’s detailed <strong>and</strong><br />

complex system of regulation of cell growth <strong>and</strong> death. Changes in gene activities<br />

are further influenced by the microenvironment within <strong>and</strong> in the vicinity of<br />

tumor cells as well as by exogenous factors. When one combines all of these<br />

aspects with inborn genetic variations among individuals, there is every kind of<br />

reason to expect tumors to display prodigiously diverse phenotypes. Breast<br />

tumors, like most solid cancers, are heterogeneous <strong>and</strong> consist of several pathological<br />

subtypes with different histological appearances of the malignant cells <strong>and</strong><br />

different clinical presentations <strong>and</strong> outcomes, <strong>and</strong> the patients show a diverse<br />

range of responses to a given treatment. Furthermore, breast tumor tissue shows<br />

From: Methods in Molecular Biology, vol. 360, <strong>Target</strong> <strong>Discovery</strong> <strong>and</strong> <strong>Validation</strong> <strong>Reviews</strong> <strong>and</strong> <strong>Protocols</strong><br />

Volume I, Emerging Strategies for <strong>Target</strong>s <strong>and</strong> Biomarker <strong>Discovery</strong><br />

Edited by: M. Sioud © Humana Press Inc., Totowa, NJ<br />

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