{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:46:57Z","timestamp":1787060817344,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201011\u2010INBS\u20100003"],"award-info":[{"award-number":["ANR\u201011\u2010INBS\u20100003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["1557"],"award-info":[{"award-number":["1557"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["2446"],"award-info":[{"award-number":["2446"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["2667"],"award-info":[{"award-number":["2667"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,9,15]]},"abstract":"<jats:p>\n                    In humans, histiocytic sarcoma (HS) is an aggressive cancer involving histiocytes. Its rarity and heterogeneity explain that treatment remains a challenge. Sharing high clinical and histopathological similarities with human HS, the canine HS is conversely frequent in specific breeds and thus constitutes a unique spontaneous model for human HS to decipher the genetic bases and to explore therapeutic options. We identified sequence alterations in the MAPK pathway in at least 63.9% (71\/111) of HS cases with mutually exclusive\n                    <jats:italic>BRAF<\/jats:italic>\n                    (0.9%; 1\/111),\n                    <jats:italic>KRAS (<\/jats:italic>\n                    7.2%; 8\/111) and\n                    <jats:italic>PTPN11<\/jats:italic>\n                    (56.75%; 63\/111) mutations concentrated at hotspots common to human cancers. Recurrent\n                    <jats:italic>PTPN11<\/jats:italic>\n                    mutations are associated to visceral disseminated HS subtype in dogs, the most aggressive clinical presentation. We then identified\n                    <jats:italic>PTPN11<\/jats:italic>\n                    mutations in 3\/19 (15.7%) human HS patients. Thus, we propose\n                    <jats:italic>PTPN11<\/jats:italic>\n                    mutations as key events for a specific subset of human and canine HS: the visceral disseminated form. Finally, by testing drugs targeting the MAPK pathway in eight canine HS cell lines, we identified a better anti\u2010proliferation activity of MEK inhibitors than PTPN11 inhibitors in canine HS neoplastic cells. In combination, these results illustrate the relevance of naturally affected dogs in deciphering genetic mechanisms and selecting efficient targeted therapies for such rare and aggressive cancers in humans.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32991","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T07:44:35Z","timestamp":1585122275000},"page":"1657-1665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["<scp>PTPN11<\/scp>\n                    mutations in canine and human disseminated histiocytic sarcoma"],"prefix":"10.1002","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-1868","authenticated-orcid":false,"given":"Benoit","family":"H\u00e9dan","sequence":"first","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Rault","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Abadie","sequence":"additional","affiliation":[{"name":"Department of Biology, Pathology and Food Sciences Oniris, Laboniris  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Ulv\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Botherel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Devauchelle","sequence":"additional","affiliation":[{"name":"Micen Vet \u2013 Cr\u00e9teil  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Copie\u2010Bergman","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, D\u00e9partement de Pathologie Groupe Henri\u2010Mondor Albert\u2010Chenevier  Cr\u00e9teil France"},{"name":"INSERM U955, \u00c9quipe 9, Facult\u00e9 de M\u00e9decine Universit\u00e9 Paris Est Cr\u00e9teil  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard","family":"Cadieu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Parrens","sequence":"additional","affiliation":[{"name":"Department of Pathology CHU de Bordeaux, H\u00f4pital du Haut L\u00e9v\u00eaque, INSERM U1035, Universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Alten","sequence":"additional","affiliation":[{"name":"Pediatric Oncology\/Hematology University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle L.","family":"Zalcman","sequence":"additional","affiliation":[{"name":"Department of Neuropathology GHU Paris Psychiatrie Neurosciences, Sainte\u2010Anne Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Cario","sequence":"additional","affiliation":[{"name":"Pediatric Oncology\/Hematology University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gandhi","family":"Damaj","sequence":"additional","affiliation":[{"name":"Haemalology Institute, CHU de Caen and Centre Fran\u00e7ois Baclesse  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Mokhtari","sequence":"additional","affiliation":[{"name":"Sorbonne University, Inserm, CNRS, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, AP\u2010HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re \u2010 Charles Foix, Service de Neuropathologie\u2010Escourolle  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Le Loarer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centre L\u00e9on B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Coulomb\u2010Lhermine","sequence":"additional","affiliation":[{"name":"Department of Pathology Trousseau Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Derrien","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Hitte","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bachelot","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Breen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, College of Veterinary Medicine North Carolina State University, CVM Research Building  Raleigh NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gilot","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7190-120X","authenticated-orcid":false,"given":"Jean Y.","family":"Blay","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centre L\u00e9on B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Donadieu","sequence":"additional","affiliation":[{"name":"Department of Haematology APHP, Trousseau Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine CNRS\u2010University of Rennes 1, UMR6290, Institute of Genetics and Development of Rennes, SFR Biosit  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-690636"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12416"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.319"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-016-1965-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0200-x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.0078"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0913"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000880"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jhered\/esp039"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-201"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-12-0190-T"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2691"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25523"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601894"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10070505"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666181106100837"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.230375"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.08.037"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201500015"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.179150"},{"key":"e_1_2_7_22_1","first-page":"3179147","article-title":"Histiocytic sarcoma associated with coombs negative acute hemolytic anemia: a rare presentation","volume":"2016","author":"Batra S","year":"2016","journal-title":"Case Rep Oncol Med"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12404"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-12-893917"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3760"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1511490"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-1273"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2273"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.32991","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32991","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32991","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:07:47Z","timestamp":1693919267000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,8]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,9,15]]}},"alternative-id":["10.1002\/ijc.32991"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32991","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,8]]},"assertion":[{"value":"2019-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}