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nature portfolio permissions reprints privacy policy advertising nature 486 nature 455 nature social media open platform autophagy-related molecular features jak-mutant myeloproliferative neoplasms dana-farber leadership council dana-farber cancer institute paraffin-embedded tumor tissue formaldehyde fixed-paraffin embedded fresh-frozen tissue specimens paraffin-embedded tumor samples precision cancer medicine integrative high-throughput sequencing report generation toolkit springerlink instant access permissions breast cancer subtypes copy-number alterations policy knowledge-based approach pilot study genomics-driven oncology generation sequence data nih u24ca143845 grant analytical output similar facilitating data deposition frozen tumor tissue privacy hypertension-related genes lung cancer biopsies prostate cancer foundation ret gene fusions crkl gene encoding generation sequencing data clinically important genes high-throughput detection data analysis pipelines systems biology approach wes data generally dna-mutation inventory enhance cancer treatment cancer reveal classes broad genomics platform clinical cancer settings

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      headline:Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
      description:Whole-exome sequencing (WES) has emerged as a transformative technology for biological discovery, but technical difficulties have so far prevented its widespread clinical use. Here, Eliezer Van Allen and colleagues are able to perform production-scale WES on small amounts of clinically acquired formalin-fixed, paraffin-embedded tumor tissues. Using a newly created WES clinical interpretation algorithm, they apply the complete clinical WES framework prospectively to patients and demonstrate how it can be used to directly affect patient care. 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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            address:
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            type:Organization
      name:Andrey Sivachenko
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               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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      name:Michael Lawrence
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            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
               type:PostalAddress
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            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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            address:
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            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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      name:Leena Gandhi
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            name:Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
            address:
               name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
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      name:Eric S Lander
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            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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      name:Stacy W Gray
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            address:
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               type:PostalAddress
            type:Organization
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            address:
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            address:
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               type:PostalAddress
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            address:
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            address:
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               type:PostalAddress
            type:Organization
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      affiliation:
            name:Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
            address:
               name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      name:Philip Kantoff
      affiliation:
            name:Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
            address:
               name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      name:Sheila A Fisher
      affiliation:
            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      name:Stacey Gabriel
      affiliation:
            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      name:Gad Getz
      affiliation:
            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
            name:Massachusetts General Hospital, Boston, Massachusetts, USA.
            address:
               name:Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
            name:Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
            address:
               name:Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Levi A Garraway
      affiliation:
            name:Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
            address:
               name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
            name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
               type:PostalAddress
            type:Organization
      email:[email protected]
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      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Department of Genome Sciences, University of Washington, Seattle, Washington, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
      name:Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.,
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      name:Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.,
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• How much profit does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Danielle%20L%20Perrin%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en make?
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• What's the profit of https://www.nature.com/articles/nm.3559/search?author=Sara%20Marlow?
• What's the financial gain of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Sara%20Marlow?
• See how much https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Sara%20Marlow%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en makes per month
• What is the monthly revenue of https://www.nature.com/articles/nm.3559/search?author=Judit%20Jane-Valbuena?
• What's the financial intake of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Judit%20Jane-Valbuena?
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• What's the monthly money flow for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Mara%20Rosenberg?
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• What's the revenue for https://www.nature.com/articles/nm.3559/search?author=Lee%20T%20Lichtenstein?
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• What are the earnings of https://www.nature.com/articles/nm.3559/search?author=Franklin%20W%20Huang?
• How much cash flow does https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Franklin%20W%20Huang have monthly?
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• Discover the revenue of https://www.nature.com/articles/nm.3559/search?author=Jennifer%20Fostel
• What's the monthly money flow for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Jennifer%20Fostel?
• https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Jennifer%20Fostel%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en's total income per month
• See how much https://www.nature.com/articles/nm.3559/search?author=Deborah%20Farlow makes per month
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• How much does https://www.nature.com/articles/nm.3559/search?author=David%20Barbie gross monthly?
• Financial intake of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=David%20Barbie
• How much does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22David%20Barbie%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en gross monthly?
• What's the financial gain of https://www.nature.com/articles/nm.3559/search?author=Leena%20Gandhi?
• What are the earnings of https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Leena%20Gandhi?
• How much does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Leena%20Gandhi%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en generate monthly?
• How much money does https://www.nature.com/articles/nm.3559/search?author=Eric%20S%20Lander make?
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• Learn how profitable https://www.nature.com/articles/nm.3559/search?author=Stacy%20W%20Gray is on a monthly basis
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• Income figures for https://www.nature.com/articles/nm.3559/search?author=Steven%20Joffe
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• How much profit is https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Steven%20Joffe%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en making per month?
• What's the total monthly financial gain of https://www.nature.com/articles/nm.3559/search?author=Pasi%20Janne?
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• How much profit does https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Pasi%20Janne%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en generate?
• How much income does https://www.nature.com/articles/nm.3559/search?author=Judy%20Garber have?
• https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Judy%20Garber's total income per month
• What's the income generated by https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Judy%20Garber%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en each month?
• How much cash flow does https://www.nature.com/articles/nm.3559/search?author=Laura%20MacConaill have monthly?
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• What's the profit of https://www.nature.com/articles/nm.3559/search?author=Neal%20Lindeman?
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• How much money does https://www.nature.com/articles/nm.3559/search?author=Barrett%20Rollins make?
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• How much does https://www.nature.com/articles/nm.3559/search?author=Philip%20Kantoff make?
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• What is the earnings of https://scholar.google.co.uk/scholar?as_q=&num=10&btnG=Search+Scholar&as_epq=&as_oq=&as_eq=&as_occt=any&as_sauthors=%22Philip%20Kantoff%22&as_publication=&as_ylo=&as_yhi=&as_allsubj=all&hl=en?
• How much money does https://www.nature.com/articles/nm.3559/search?author=Sheila%20A%20Fisher make?
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• Discover the revenue of https://www.nature.com/articles/nm.3559/search?author=Stacey%20Gabriel
• Income figures for https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Stacey%20Gabriel
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• Learn about the earnings of https://www.nature.com/articles/nm.3559/search?author=Gad%20Getz
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• What's the income of https://www.nature.com/articles/nm.3559/search?author=Levi%20A%20Garraway?
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• Financial intake of https://www.nature.com/articles/nm.3559/mailto:[email protected]
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• Financial intake of https://s100.copyright.com/AppDispatchServlet?title=Whole-exome%20sequencing%20and%20clinical%20interpretation%20of%20formalin-fixed%2C%20paraffin-embedded%20tumor%20samples%20to%20guide%20precision%20cancer%20medicine&author=Eliezer%20M%20Van%20Allen%20et%20al&contentID=10.1038%2Fnm.3559©right=Springer%20Nature%20America%2C%20Inc.&publication=1078-8956&publicationDate=2014-05-18&publisherName=SpringerNature&orderBeanReset=true
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