NATURE MEDICINE | TECHNICAL REPORT
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Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
Eliezer M Van Allen, Nikhil Wagle, Petar Stojanov, Danielle L Perrin, Kristian Cibulskis, Sara Marlow, Judit Jane-Valbuena, Dennis C Friedrich, Gregory Kryukov, Scott L Carter, Aaron McKenna, Andrey Sivachenko, Mara Rosenberg, Adam Kiezun, Douglas Voet, Michael Lawrence, Lee T Lichtenstein, Jeff G Gentry, Franklin W Huang, Jennifer Fostel, Deborah Farlow, David Barbie, Leena Gandhi, Eric S Lander, Stacy W Gray et al.
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Nature Medicine (2014) doi:10.1038/nm.3559
Received 19 April 2013 Accepted 14 October 2013 Published online 18 May 2014
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Abstract
Abstract• References• Author information• Supplementary information
Translating whole-exome sequencing (WES) for prospective clinical use may have an impact on the care of patients with cancer; however, multiple innovations are necessary for clinical implementation. These include rapid and robust WES of DNA derived from formalin-fixed, paraffin-embedded tumor tissue, analytical output similar to data from frozen samples and clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival formalin-fixed, paraffin-embedded tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a 'long tail' of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15 out of 16 patients. In one patient, previously undetected findings guided clinical trial enrollment, leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
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