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.
Description
Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine : Nature Medicine : Nature Research
%0 Journal Article
%1 vanallen2014wholeexome
%A Van Allen, Eliezer M
%A Wagle, Nikhil
%A Stojanov, Petar
%A Perrin, Danielle L
%A Cibulskis, Kristian
%A Marlow, Sara
%A Jane-Valbuena, Judit
%A Friedrich, Dennis C
%A Kryukov, Gregory
%A Carter, Scott L
%A McKenna, Aaron
%A Sivachenko, Andrey
%A Rosenberg, Mara
%A Kiezun, Adam
%A Voet, Douglas
%A Lawrence, Michael
%A Lichtenstein, Lee T
%A Gentry, Jeff G
%A Huang, Franklin W
%A Fostel, Jennifer
%A Farlow, Deborah
%A Barbie, David
%A Gandhi, Leena
%A Lander, Eric S
%A Gray, Stacy W
%A Joffe, Steven
%A Janne, Pasi
%A Garber, Judy
%A MacConaill, Laura
%A Lindeman, Neal
%A Rollins, Barrett
%A Kantoff, Philip
%A Fisher, Sheila A
%A Gabriel, Stacey
%A Getz, Gad
%A Garraway, Levi A
%D 2014
%I Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
%J Nat Med
%K PAYWALL WES broad precision-medicine sequencing
%N 6
%P 682--688
%T Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
%U http://dx.doi.org/10.1038/nm.3559
%V 20
%X 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.
@article{vanallen2014wholeexome,
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.},
added-at = {2017-07-22T10:28:12.000+0200},
author = {Van Allen, Eliezer M and Wagle, Nikhil and Stojanov, Petar and Perrin, Danielle L and Cibulskis, Kristian and Marlow, Sara and Jane-Valbuena, Judit and Friedrich, Dennis C and Kryukov, Gregory and Carter, Scott L and McKenna, Aaron and Sivachenko, Andrey and Rosenberg, Mara and Kiezun, Adam and Voet, Douglas and Lawrence, Michael and Lichtenstein, Lee T and Gentry, Jeff G and Huang, Franklin W and Fostel, Jennifer and Farlow, Deborah and Barbie, David and Gandhi, Leena and Lander, Eric S and Gray, Stacy W and Joffe, Steven and Janne, Pasi and Garber, Judy and MacConaill, Laura and Lindeman, Neal and Rollins, Barrett and Kantoff, Philip and Fisher, Sheila A and Gabriel, Stacey and Getz, Gad and Garraway, Levi A},
biburl = {https://www.bibsonomy.org/bibtex/2fc7ac0cf23e65b9a190eb56e0f7084f9/marcsaric},
description = {Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine : Nature Medicine : Nature Research},
interhash = {62be6855cd1a6a96208c66330d1750da},
intrahash = {fc7ac0cf23e65b9a190eb56e0f7084f9},
issn = {10788956},
journal = {Nat Med},
keywords = {PAYWALL WES broad precision-medicine sequencing},
month = jun,
number = 6,
pages = {682--688},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
timestamp = {2017-07-22T10:28:12.000+0200},
title = {Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine},
url = {http://dx.doi.org/10.1038/nm.3559},
volume = 20,
year = 2014
}