Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine
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...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/96682 |
| _version_ | 1826218069920317440 |
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| author | Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven |
| author_sort | Lander, Eric Steven |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:13:40Z |
| format | Article |
| id | mit-1721.1/96682 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:13:40Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/966822022-10-03T11:14:10Z Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. 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. National Cancer Institute (U.S.) (Grant 1U24CA126546) 2015-04-17T19:00:16Z 2015-04-17T19:00:16Z 2014-05 2013-04 Article http://purl.org/eprint/type/JournalArticle 1078-8956 1546-170X http://hdl.handle.net/1721.1/96682 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. en_US http://dx.doi.org/10.1038/nm.3559 Nature Medicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Lander, Eric Steven Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title | Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title_full | Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title_fullStr | Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title_full_unstemmed | Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title_short | Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine |
| title_sort | whole exome sequencing and clinical interpretation of ffpe tumor samples to guide precision cancer medicine |
| url | http://hdl.handle.net/1721.1/96682 |
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