Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine
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Lander_Whole-exone.pdf
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1.41 MB
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15b8188b16ea070ae587e63ea560e652
Author(s)
Lander, Eric Steven
Alternative Title
Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
Date Issued
May 2014
Journal
Nature Medicine
Publisher
Nature Publishing Group
Citation
Van Allen, Eliezer M, Nikhil Wagle, Petar Stojanov, Danielle L Perrin, Kristian Cibulskis, Sara Marlow, Judit Jane-Valbuena, et al. “Whole-Exome Sequencing and Clinical Interpretation of Formalin-Fixed, Paraffin-Embedded Tumor Samples to Guide Precision Cancer Medicine.” Nature Medicine 20, no. 6 (May 18, 2014): 682–688.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/nm.3559
