An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species
Luca Morandi,
Silvia Sabattini,
Andrea Renzi,
Antonella Rigillo,
Giuliano Bettini,
Eva Dervas,
Alexandria Schauer,
Marco Morandi,
Davide B. Gissi,
Achille Tarsitano,
Stefania Evangelisti,
Caterina Tonon
Affiliations
Luca Morandi
Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy
Silvia Sabattini
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy
Andrea Renzi
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy
Antonella Rigillo
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy
Giuliano Bettini
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy
Eva Dervas
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
Alexandria Schauer
Institute of Veterinary Pathology, Vetsuisse Faculty, University of Bern, 8466 Bern, Switzerland
Marco Morandi
Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy
Davide B. Gissi
Section of Oral Science, Department of Biomedical and Neuromuscular Sciences, University of Bologna, 40125 Bologna, Italy
Achille Tarsitano
Unit of Oral and Maxillofacial Surgery, Azienda Ospedaliero-Universitaria di Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40138 Bologna, Italy
Stefania Evangelisti
Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy
Caterina Tonon
Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy
Background: Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. Methods: Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were collected as normal controls. Bisulfite next generation sequencing evaluated the DNA methylation level from seven UCNEs (uc.160, uc.283, uc.416, uc.339, uc.270, uc.299, and uc.328). Results: 57/59 CpGs were significantly different according to the Kruskal–Wallis test (p < 0.05) comparing normal samples with SCC. A common DNA hypermethylation pattern was observed in SCCs from all the species evaluated in this study, with an increasing trend of hypermethylation starting from normal mucosa, through stomatitis to SCC. Conclusions: Our findings indicate that UCNEs are hypermethylated in human SCC, and this behavior is also conserved among different species of mammals.
