Transcriptome sequencing reveals two subtypes of cortisol‐secreting adrenocortical tumours in dogs and identifies CYP26B1 as a potential new therapeutic target. (16th January 2023)

• Record Type: Journal Article
• Authors: Sanders, Karin; Kooistra, Hans S.; van den Heuvel, Marieke; Mokry, Michal; Grinwis, Guy C. M.; van den Dungen, Noortje A. M.; van Steenbeek, Frank G.; Galac, Sara
• Is Part Of: Veterinary and comparative oncology. Volume 21:Number 1(2023)
• Page Start: 100
• Page End: 110
• Publication Date: 2023-01-16
• Subjects: adrenocortical carcinoma -- canine diseases -- Cushing's syndrome -- RNA‐seq; Veterinary oncology -- Periodicals; Neoplasms -- veterinary -- Periodicals; 636.0896994005
• DOI: 10.1111/vco.12871
• Languages: English
• ISSNs: 1476-5810

Abstract

Abstract: Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%–20% of cases, CS is caused by a cortisol‐secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs ( n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p ‐value was <.05 and the log2 fold change was >2 or < −2. 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 ( p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 ( CYP26B1 ), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol‐secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher ( p = .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.