European Journal of Radiology 70 (2009) 232–241 Contents lists available at ScienceDirect European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging Aaron M. Rutman a , Michael D. Kuo a,b,* a Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103, USA b Center for Translational Medical Systems, University of California San Diego Medical Center, San Diego, CA 92103, USA article info Article history: Received 13 January 2009 Accepted 14 January 2009 Keywords: Radiogenomics Personalized medicine Diagnostic imaging abstract Studies employing high-throughput biological techniques have recently contributed to an improved char- acterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things lim- its the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of vari- ous forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as “radiogenomics.” These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction With the relatively recent advent of high-throughput biological methods, biomedical research has seen many changes. High- throughput tools are able to provide a global snapshot of cellular physiology, allowing massively parallel assessment of thousands of genes and gene products. Gene expression profiling of various human tissues has led to a better understanding of cellular path- ways and various pathological conditions on a biomolecular level. Analysis of different cancerous tissues in relation to samples of normal organ tissue has permitted an enhanced understanding of tumorogenic processes and aided in improved staging and sub- classification of various malignancies. Numerous studies have also shown that gene expression signatures, each comprised of dozens to hundreds of genes, can significantly improve diagnostic classifi- cation, prognostication, and prediction of therapeutic response in cancer [1–6]. However, gene expression profiling is dependent on the surgi- cal procurement of tissue, yielding a host of risks and potential complications, and making it an unrealistic option for every cancer * Corresponding author at: Center for Translational Medical Systems, University of California San Diego Medical Center, San Diego, CA 92103, USA. Tel.: +1 619 543 6607; fax: +1 619 543 3781. E-mail address: mkuo@ucsd.edu (M.D. Kuo). patient. In contrast to genetic profiling studies, radiographic imag- ing studies are part of routine clinical care. While it is accepted that imaging can provide important anatomical and morphologi- cal information, it is not perceived to imply much consequential molecular detail. However, several studies have recently intro- duced novel methods for correlating unique features of tumor morphology and physiology garnered through non-invasive imag- ing with specific patterns of gene expression on a genome-wide scale, thereby introducing the field of “radiogenomics” [7–9]. These researchers propose that specific radiological tumor phenotypes, or “radiophenotypes,” can serve as surrogates for gene expression sig- natures, informing a non-invasive yet accurate diagnosis of tumor subtype and molecular biology. Further, if imaging traits can be associated with previously determined treatment-response gene- expression patterns, then non-invasive, routine clinical studies can inform the likely response to specific chemotherapeutics and aid in the decision making process towards an optimal form and dura- tion of treatment. Such methods will potentially allow diagnostic imaging to augment or supplant current techniques that utilize surgical biopsy and pathohistologic analysis, and contribute to a shift towards a more fundamental genetic-based and personalized medicine. The following discussion will center on the promise of high-throughput biological techniques and the emerging field of radiogenomics—an emerging technology that has the potential to link high-throughput molecular diagnostics and diagnostic imag- ing. 0720-048X/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2009.01.050