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Open Access Research article

A methodology for utilization of predictive genomic signatures in FFPE samples

Jennifer A Freedman1, Christina K Augustine2, Angelica M Selim6, Kirsten C Holshausen3, Zhengzheng Wei1, Katherine A Tsamis1, David S Hsu3, Holly K Dressman1, William T Barry4, Douglas S Tyler2 and Joseph R Nevins15*

Author Affiliations

1 Institute for Genome Sciences and Policy, Duke University Medical Center, DUMC Box 3382, Durham, 27708, USA

2 Department of Surgery, Duke University Medical Center, DUMC Box 3704, Durham, 27710, USA

3 Department of Medicine, Duke University Medical Center, DUMC Box 3230, Durham, 27710, USA

4 Department of Biostatistics and Bioinformatics, Duke University Medical Center, DUMC Box 2721, Durham, 27710, USA

5 Department of Molecular Genetics and Microbiology, Duke University Medical Center, DUMC Box 3054, Durham, 27710, USA

6 Department of Pathology Clinical Services, Duke University Medical Center, DUMC Box 3712, Durham, 27710, USA

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BMC Medical Genomics 2011, 4:58  doi:10.1186/1755-8794-4-58

Published: 11 July 2011

Abstract

Background

Gene expression signatures developed to measure the activity of oncogenic signaling pathways have been used to dissect the heterogeneity of tumor samples and to predict sensitivity to various cancer drugs that target components of the relevant pathways, thus potentially identifying therapeutic options for subgroups of patients. To facilitate broad use, including in a clinical setting, the ability to generate data from formalin-fixed, paraffin-embedded (FFPE) tissues is essential.

Methods

Patterns of pathway activity in matched fresh-frozen and FFPE xenograft tumor samples were generated using the MessageAmp Premier methodology in combination with assays using Affymetrix arrays. Results generated were compared with those obtained from fresh-frozen samples using a standard Affymetrix assay. In addition, gene expression data from patient matched fresh-frozen and FFPE melanomas were also utilized to evaluate the consistency of predictions of oncogenic signaling pathway status.

Results

Significant correlation was observed between pathway activity predictions from paired fresh-frozen and FFPE xenograft tumor samples. In addition, significant concordance of pathway activity predictions was also observed between patient matched fresh-frozen and FFPE melanomas.

Conclusions

Reliable and consistent predictions of oncogenic pathway activities can be obtained from FFPE tumor tissue samples. The ability to reliably utilize FFPE patient tumor tissue samples for genomic analyses will lead to a better understanding of the biology of disease progression and, in the clinical setting, will provide tools to guide the choice of therapeutics to those most likely to be effective in treating a patient's disease.