1. ¹Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC, USA
2. ²Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
3. ³Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan

Correspondence: Professor JR Nevins, Duke Institute for Genome Sciences and Policy, 2123 CIEMAS, Duke University Medical Center, Durham, NC 27708, USA. E-mail: j.nevins@duke.edu

⁴Current address: Genomic Oncology Programme, Cancer Science Institute Singapore, National University of Singapore, Singapore 117456.

Received 15 December 2008; Revised 12 March 2009; Accepted 8 April 2009; Published online 1 June 2009.

Abstract

The oncogenic phenotype is complex, resulting from the accumulation of multiple somatic mutations that lead to the deregulation of growth regulatory and cell fate controlling activities and pathways. The ability to dissect this complexity, so as to reveal discrete aspects of the biology underlying the oncogenic phenotype, is critical to understanding the various mechanisms of disease as well as to reveal opportunities for novel therapeutic strategies. Previous work has characterized the process of anchorage-independent growth of cancer cells in vitro as a key aspect of the tumor phenotype, particularly with respect to metastatic potential. Nevertheless, it remains a major challenge to translate these cell biology findings into the context of human tumors. We previously used DNA microarray assays to develop expression signatures, which have the capacity to identify subtle distinctions in biological states and can be used to connect in vitro and in vivo states. Here we describe the development of a signature of anchorage-independent growth, show that the signature exhibits characteristics of deregulated mitochondrial function and then demonstrate that the signature identifies human tumors with the potential for metastasis.