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To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (<jats:italic>n<\/jats:italic>\u00a0=\u200948) and normal adrenal cortices (NACs; <jats:italic>n<\/jats:italic>\u00a0=\u200910) of dogs. A gene was declared differentially expressed when the adjusted <jats:italic>p<\/jats:italic>\u2010value was &lt;.05 and the log<jats:sub>2<\/jats:sub> fold change was &gt;2 or\u2009&lt;\u2009\u22122. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (<jats:italic>p<\/jats:italic>\u00a0=\u2009.002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (<jats:italic>CYP26B1<\/jats:italic>), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol\u2010secreting adrenocortical carcinomas. In the validation cohort, <jats:italic>CYP26B1<\/jats:italic> was also expressed significantly higher (<jats:italic>p<\/jats:italic>\u00a0=\u2009.012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.<\/jats:p>","DOI":"10.1111\/vco.12871","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T06:09:39Z","timestamp":1672380579000},"page":"100-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptome sequencing reveals two subtypes of cortisol\u2010secreting adrenocortical tumours in dogs and identifies <scp>CYP26B1<\/scp> as a potential new therapeutic target"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-9853","authenticated-orcid":false,"given":"Karin","family":"Sanders","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University  Utrecht The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-0492","authenticated-orcid":false,"given":"Hans S.","family":"Kooistra","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michal","family":"Mokry","sequence":"additional","affiliation":[{"name":"Central Diagnostics Laboratory University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory of Experimental Cardiology, Department of Cardiology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-9648","authenticated-orcid":false,"given":"Guy C. 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