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 FFPE tumor samples to guide precision cancer medicine
%0 Journal Article
%1 VanAllen:2014:Nat-Med:24836576
%A Van Allen, E M
%A Wagle, N
%A Stojanov, P
%A Perrin, D L
%A Cibulskis, K
%A Marlow, S
%A Jane-Valbuena, J
%A Friedrich, D C
%A Kryukov, G
%A Carter, S L
%A McKenna, A
%A Sivachenko, A
%A Rosenberg, M
%A Kiezun, A
%A Voet, D
%A Lawrence, M
%A Lichtenstein, L T
%A Gentry, J G
%A Huang, F W
%A Fostel, J
%A Farlow, D
%A Barbie, D
%A Gandhi, L
%A Lander, E S
%A Gray, S W
%A Joffe, S
%A Janne, P
%A Garber, J
%A MacConaill, L
%A Lindeman, N
%A Rollins, B
%A Kantoff, P
%A Fisher, S A
%A Gabriel, S
%A Getz, G
%A Garraway, L A
%D 2014
%J Nat Med
%K FFPE MUSTREAD dna-sequencing exome fulltext sequencing wes
%N 6
%P 682-688
%R 10.1038/nm.3559
%T Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048335/
%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{VanAllen:2014:Nat-Med:24836576,
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 = {2017-10-03T11:03:40.000+0200},
author = {Van Allen, E M and Wagle, N and Stojanov, P and Perrin, D L and Cibulskis, K and Marlow, S and Jane-Valbuena, J and Friedrich, D C and Kryukov, G and Carter, S L and McKenna, A and Sivachenko, A and Rosenberg, M and Kiezun, A and Voet, D and Lawrence, M and Lichtenstein, L T and Gentry, J G and Huang, F W and Fostel, J and Farlow, D and Barbie, D and Gandhi, L and Lander, E S and Gray, S W and Joffe, S and Janne, P and Garber, J and MacConaill, L and Lindeman, N and Rollins, B and Kantoff, P and Fisher, S A and Gabriel, S and Getz, G and Garraway, L A},
biburl = {https://www.bibsonomy.org/bibtex/29833a857c8c7933bd98313ee1bf4f094/marcsaric},
description = {Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine},
doi = {10.1038/nm.3559},
interhash = {62be6855cd1a6a96208c66330d1750da},
intrahash = {9833a857c8c7933bd98313ee1bf4f094},
journal = {Nat Med},
keywords = {FFPE MUSTREAD dna-sequencing exome fulltext sequencing wes},
month = jun,
number = 6,
pages = {682-688},
pmid = {24836576},
timestamp = {2017-10-03T11:03:40.000+0200},
title = {Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048335/},
volume = 20,
year = 2014
}