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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>RAS</italic> Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors</title><author><name sortKey="Oberholzer, Patrick A" sort="Oberholzer, Patrick A" uniqKey="Oberholzer P" first="Patrick A." last="Oberholzer">Patrick A. Oberholzer</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Kee, Damien" sort="Kee, Damien" uniqKey="Kee D" first="Damien" last="Kee">Damien Kee</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Dziunycz, Piotr" sort="Dziunycz, Piotr" uniqKey="Dziunycz P" first="Piotr" last="Dziunycz">Piotr Dziunycz</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Sucker, Antje" sort="Sucker, Antje" uniqKey="Sucker A" first="Antje" last="Sucker">Antje Sucker</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Kamsukom, Nyam" sort="Kamsukom, Nyam" uniqKey="Kamsukom N" first="Nyam" last="Kamsukom">Nyam Kamsukom</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Jones, Robert" sort="Jones, Robert" uniqKey="Jones R" first="Robert" last="Jones">Robert Jones</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Roden, Christine" sort="Roden, Christine" uniqKey="Roden C" first="Christine" last="Roden">Christine Roden</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Chalk, Clinton J" sort="Chalk, Clinton J" uniqKey="Chalk C" first="Clinton J." last="Chalk">Clinton J. Chalk</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Ardlie, Kristin" sort="Ardlie, Kristin" uniqKey="Ardlie K" first="Kristin" last="Ardlie">Kristin Ardlie</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Palescandolo, Emanuele" sort="Palescandolo, Emanuele" uniqKey="Palescandolo E" first="Emanuele" last="Palescandolo">Emanuele Palescandolo</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Piris, Adriano" sort="Piris, Adriano" uniqKey="Piris A" first="Adriano" last="Piris">Adriano Piris</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Macconaill, Laura E" sort="Macconaill, Laura E" uniqKey="Macconaill L" first="Laura E." last="Macconaill">Laura E. Macconaill</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Hofbauer, Gunther F L" sort="Hofbauer, Gunther F L" uniqKey="Hofbauer G" first="Günther F. L." last="Hofbauer">Günther F. L. Hofbauer</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Schadendorf, Dirk" sort="Schadendorf, Dirk" uniqKey="Schadendorf D" first="Dirk" last="Schadendorf">Dirk Schadendorf</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Garraway, Levi A" sort="Garraway, Levi A" uniqKey="Garraway L" first="Levi A." last="Garraway">Levi A. Garraway</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22067401</idno><idno type="pmc">3269955</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269955</idno><idno type="RBID">PMC:3269955</idno><idno type="doi">10.1200/JCO.2011.36.7680</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001941</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001941</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>RAS</italic> Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors</title><author><name sortKey="Oberholzer, Patrick A" sort="Oberholzer, Patrick A" uniqKey="Oberholzer P" first="Patrick A." last="Oberholzer">Patrick A. Oberholzer</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Kee, Damien" sort="Kee, Damien" uniqKey="Kee D" first="Damien" last="Kee">Damien Kee</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Dziunycz, Piotr" sort="Dziunycz, Piotr" uniqKey="Dziunycz P" first="Piotr" last="Dziunycz">Piotr Dziunycz</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Sucker, Antje" sort="Sucker, Antje" uniqKey="Sucker A" first="Antje" last="Sucker">Antje Sucker</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Kamsukom, Nyam" sort="Kamsukom, Nyam" uniqKey="Kamsukom N" first="Nyam" last="Kamsukom">Nyam Kamsukom</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Jones, Robert" sort="Jones, Robert" uniqKey="Jones R" first="Robert" last="Jones">Robert Jones</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Roden, Christine" sort="Roden, Christine" uniqKey="Roden C" first="Christine" last="Roden">Christine Roden</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Chalk, Clinton J" sort="Chalk, Clinton J" uniqKey="Chalk C" first="Clinton J." last="Chalk">Clinton J. Chalk</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Ardlie, Kristin" sort="Ardlie, Kristin" uniqKey="Ardlie K" first="Kristin" last="Ardlie">Kristin Ardlie</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Palescandolo, Emanuele" sort="Palescandolo, Emanuele" uniqKey="Palescandolo E" first="Emanuele" last="Palescandolo">Emanuele Palescandolo</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Piris, Adriano" sort="Piris, Adriano" uniqKey="Piris A" first="Adriano" last="Piris">Adriano Piris</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Macconaill, Laura E" sort="Macconaill, Laura E" uniqKey="Macconaill L" first="Laura E." last="Macconaill">Laura E. Macconaill</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Hofbauer, Gunther F L" sort="Hofbauer, Gunther F L" uniqKey="Hofbauer G" first="Günther F. L." last="Hofbauer">Günther F. L. Hofbauer</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A." last="Mcarthur">Grant A. Mcarthur</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Schadendorf, Dirk" sort="Schadendorf, Dirk" uniqKey="Schadendorf D" first="Dirk" last="Schadendorf">Dirk Schadendorf</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author><author><name sortKey="Garraway, Levi A" sort="Garraway, Levi A" uniqKey="Garraway L" first="Levi A." last="Garraway">Levi A. Garraway</name><affiliation><nlm:aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Clinical Oncology</title><idno type="ISSN">0732-183X</idno><idno type="eISSN">1527-7755</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>RAF inhibitors are effective against melanomas with <italic>BRAF</italic> V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation.</p></sec><sec><title>Methods</title><p>Four international centers contributed 237 KA or cSCC tumor samples from patients receiving an RAF inhibitor (either vemurafenib or sorafenib; n = 19) or immunosuppression therapy (n = 53) or tumors that developed spontaneously (n = 165). Each sample was profiled for 396 known somatic mutations across 33 cancer-related genes by using a mass spectrometric–based genotyping platform.</p></sec><sec><title>Results</title><p>Mutations were detected in 16% of tumors (38 of 237), with five tumors harboring two mutations. Mutations in <italic>TP53</italic>, <italic>CDKN2A</italic>, <italic>HRAS</italic>, <italic>KRAS</italic>, and <italic>PIK3CA</italic> were previously described in squamous cell tumors. Mutations in <italic>MYC</italic>, <italic>FGFR3</italic>, and <italic>VHL</italic> were identified for the first time. A higher frequency of activating <italic>RAS</italic> mutations was found in tumors from patients treated with an RAF inhibitor versus populations treated with a non–RAF inhibitor (21.1% <italic>v</italic> 3.2%; <italic>P</italic> < .01), although overall mutation rates between treatment groups were similar (RAF inhibitor, 21.1%; immunosuppression, 18.9%; and spontaneous, 17.6%; <italic>P</italic> = not significant). Tumor histology (KA <italic>v</italic> cSCC), tumor site (head and neck <italic>v</italic> other), patient age (≤ 70 <italic>v</italic> > 70 years), and sex had no significant impact on mutation rate or type.</p></sec><sec><title>Conclusion</title><p>Squamous cell tumors from patients treated with an RAF inhibitor have a distinct mutational profile that supports a mechanism of therapy-induced tumorigenesis in <italic>RAS</italic>-primed cells. Conceivably, cotargeting of MEK together with RAF may reduce or prevent formation of these tumors.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Oncol</journal-id><journal-id journal-id-type="hwp">jco</journal-id><journal-id journal-id-type="pmc">jco</journal-id><journal-id journal-id-type="publisher-id">JCO</journal-id><journal-title-group><journal-title>Journal of Clinical Oncology</journal-title></journal-title-group><issn pub-type="ppub">0732-183X</issn><issn pub-type="epub">1527-7755</issn><publisher><publisher-name>American Society of Clinical Oncology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22067401</article-id><article-id pub-id-type="pmc">3269955</article-id><article-id pub-id-type="publisher-id">67680</article-id><article-id pub-id-type="doi">10.1200/JCO.2011.36.7680</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>Epid1</subject><subject>Mela5</subject><subject>Mela7</subject><subject>Nmel</subject><subject>To8</subject><subject>To11</subject></subj-group><subj-group subj-group-type="heading"><subject>Original Reports</subject><subj-group><subject>Translational Oncology</subject></subj-group></subj-group></article-categories><title-group><article-title><italic>RAS</italic> Mutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors</article-title><alt-title alt-title-type="short">Skin Tumors Developed on <italic>BRAF</italic> Therapy Have Frequent <italic>RAS</italic> Mutations</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Oberholzer</surname><given-names>Patrick A.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Kee</surname><given-names>Damien</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Dziunycz</surname><given-names>Piotr</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Sucker</surname><given-names>Antje</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Kamsukom</surname><given-names>Nyam</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Roden</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Chalk</surname><given-names>Clinton J.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Ardlie</surname><given-names>Kristin</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Palescandolo</surname><given-names>Emanuele</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Piris</surname><given-names>Adriano</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>MacConaill</surname><given-names>Laura E.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Robert</surname><given-names>Caroline</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Hofbauer</surname><given-names>Günther F.L.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>McArthur</surname><given-names>Grant A.</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Schadendorf</surname><given-names>Dirk</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Garraway</surname><given-names>Levi A.</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="corresp" rid="cor1"></xref></contrib><aff id="aff1">Patrick A. Oberholzer, Clinton J. Chalk, Kristin Ardlie, Laura E. MacConaill, and Levi A. Garraway, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Patrick A. Oberholzer, Robert Jones, Christine Roden, Emanuele Palescandolo, and Laura E. MacConaill, Dana-Farber Cancer Institute; Adriano Piris, Massachusetts General Hospital; Adriano Piris, Harvard Medical School, Boston, MA; Damien Kee and Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; Damien Kee, University of Melbourne, Parkville, Australia; Piotr Dziunycz and Günther F.L. Hofbauer, University Hospital Zürich, Zürich, Switzerland; Antje Sucker and Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Nyam Kamsukom and Caroline Robert, Gustave Roussy Institute and L'Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Villejuif, France.</aff></contrib-group><author-notes><fn fn-type="equal"><p>P.A.O., D.K., D.S., and L.A.G. contributed equally to this study.</p></fn><corresp id="cor1">Corresponding author: Levi A. Garraway, MD, PhD, Broad Institute of MIT and Harvard, Dana Building, Room 1542, 44 Binney St, Boston, MA 02115; e-mail: <email>levi_garraway@dfci.harvard.edu</email>.</corresp></author-notes><pub-date pub-type="ppub"><day>20</day><month>1</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>7</day><month>11</month><year>2011</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>1</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>30</volume><issue>3</issue><fpage>316</fpage><lpage>321</lpage><history><date date-type="received"><day>28</day><month>4</month><year>2011</year></date><date date-type="accepted"><day>18</day><month>7</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 by American Society of Clinical Oncology</copyright-statement><copyright-year>2011</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zlj00312000316.pdf"></self-uri><abstract><sec><title>Purpose</title><p>RAF inhibitors are effective against melanomas with <italic>BRAF</italic> V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation.</p></sec><sec><title>Methods</title><p>Four international centers contributed 237 KA or cSCC tumor samples from patients receiving an RAF inhibitor (either vemurafenib or sorafenib; n = 19) or immunosuppression therapy (n = 53) or tumors that developed spontaneously (n = 165). Each sample was profiled for 396 known somatic mutations across 33 cancer-related genes by using a mass spectrometric–based genotyping platform.</p></sec><sec><title>Results</title><p>Mutations were detected in 16% of tumors (38 of 237), with five tumors harboring two mutations. Mutations in <italic>TP53</italic>, <italic>CDKN2A</italic>, <italic>HRAS</italic>, <italic>KRAS</italic>, and <italic>PIK3CA</italic> were previously described in squamous cell tumors. Mutations in <italic>MYC</italic>, <italic>FGFR3</italic>, and <italic>VHL</italic> were identified for the first time. A higher frequency of activating <italic>RAS</italic> mutations was found in tumors from patients treated with an RAF inhibitor versus populations treated with a non–RAF inhibitor (21.1% <italic>v</italic> 3.2%; <italic>P</italic> < .01), although overall mutation rates between treatment groups were similar (RAF inhibitor, 21.1%; immunosuppression, 18.9%; and spontaneous, 17.6%; <italic>P</italic> = not significant). Tumor histology (KA <italic>v</italic> cSCC), tumor site (head and neck <italic>v</italic> other), patient age (≤ 70 <italic>v</italic> > 70 years), and sex had no significant impact on mutation rate or type.</p></sec><sec><title>Conclusion</title><p>Squamous cell tumors from patients treated with an RAF inhibitor have a distinct mutational profile that supports a mechanism of therapy-induced tumorigenesis in <italic>RAS</italic>-primed cells. Conceivably, cotargeting of MEK together with RAF may reduce or prevent formation of these tumors.</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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