{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:26:47Z","timestamp":1790008007934,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007709","name":"Michigan State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007709","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Comparative Oncology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>\n                    Histiocytic sarcoma (HS) is an aggressive malignant neoplasm of dendritic cell origin that is common in certain breeds of dogs. High prevalence of fatal, disseminated HS has been described in Bernese Mountain Dogs (BMDs). Support for genetic predisposition to develop HS has been presented in several studies, but to date, causative genetic events have not been reported. In addition, no driver mutations have been identified in tumours. Recently, E76K gain\u2010of\u2010function mutation in SHP2 encoded by the\n                    <jats:italic>PTPN11<\/jats:italic>\n                    gene has been described in human histiocytic malignancies. In our study, we identified the PTPN11\n                    <jats:sup>E76K<\/jats:sup>\n                    in HS of BMDs. Amplification of exon 3 of the\n                    <jats:italic>PTPN11<\/jats:italic>\n                    gene followed by Sanger sequencing was used to detect the mutation and estimate the prevalence in HS from 30 BMDs, 13 Golden Retrievers and 10 other dog breeds. The overall prevalence of PTPN11\n                    <jats:sup>E76K<\/jats:sup>\n                    in HS of BMDs was 36.67% compared with 8.69% in other breeds. No mutation was identified in normal tissues from 10 BMDs with HS that carried the mutation and 12 control dogs with no neoplastic disease, including 6 BMDs. Increased immunoreactivity for AKT, phosphorylated ERK1\/2 and phosphorylated AKT in a small subset of BMDs with PTPN11\n                    <jats:sup>E76K<\/jats:sup>\n                    suggests that a gain\u2010of\u2010function might be mediated by the ERK and AKT pathways. These data suggest PTPN11\n                    <jats:sup>E76K<\/jats:sup>\n                    as an important driver mutation of HS in BMDs. This information may not only aid in unravelling the tumourigenic events associated with HS in BMDs, but also help in identifying more promising therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/vco.12357","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T04:48:36Z","timestamp":1505882916000},"page":"220-228","source":"Crossref","is-referenced-by-count":31,"title":["Gain\u2010of\u2010function mutation in\n                    <i>PTPN11<\/i>\n                    in histiocytic sarcomas of Bernese Mountain Dogs"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9389-4490","authenticated-orcid":false,"given":"T.","family":"Thaiwong","sequence":"first","affiliation":[{"name":"Veterinary Diagnostic Laboratory Michigan State University  Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sirivisoot","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Laboratory Michigan State University  Lansing Michigan"},{"name":"Department of Pathology, Faculty of Veterinary Sciences Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine Michigan State University  East Lansing Michigan"},{"name":"Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine Michigan State University  East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Yuzbasiyan\u2010Gurkan","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences, College of Veterinary Medicine Michigan State University  East Lansing Michigan"},{"name":"Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine Michigan State University  East Lansing Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kiupel","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Laboratory Michigan State University  Lansing Michigan"},{"name":"Comparative Medicine and Integrative Biology Program, College of Veterinary Medicine Michigan State University  East Lansing Michigan"},{"name":"Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine Michigan State University  East Lansing 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