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Cells2020; 9(9); 2092; doi: 10.3390/cells9092092

An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species.

Abstract: 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. 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). 57/59 CpGs were significantly different according to the Kruskal-Wallis test ( < 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. Our findings indicate that UCNEs are hypermethylated in human SCC, and this behavior is also conserved among different species of mammals.
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Publication Date: 2020-09-13 PubMed ID: 32933205PubMed Central: PMC7565279DOI: 10.3390/cells9092092Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines changes in DNA methylation of certain genomic sequences (Ultra-conserved non-coding elements or UCNEs) in skin cancer (squamous cell carcinoma) in different mammals. The researchers discovered a common trend of increased methylation in skin cancer across all studied species, suggesting these DNA sequences are crucial in the development of this cancer.

Understanding DNA Methylation and UCNEs

  • DNA methylation is a biological process that alters the activity of the DNA, impacting how genes control cellular functions, and often plays a role in the growth of cancer cells.
  • Ultra-conserved non-coding elements (UCNEs) are segments of DNA that remain very similar across different species, highlighting their likely critical role in biological functions.
  • Before this research, UCNEs were already suspected to play a role in cancer development.

Objectives of the Study

  • The primary goal of the study was to inspect changes in DNA methylation within UCNEs in Squamous Cell Carcinoma (SCC), a common type of skin cancer, across various mammalian species.

Study Design and Method

  • The study used a wide variety of SCC samples from different species, including humans, cats, dogs, a horse, a bovine, a badger and a porcupine.
  • It also used control samples from healthy individuals of these species, and from cats with feline stomatitis, a disease that is non-malignant but inflammatory (like cancer).
  • The DNA methylation level in seven specific UCNEs were examined using a technique called bisulfite next generation sequencing.

Findings and Analysis

  • The researchers found significantly different levels of DNA methylation in the cancerous samples as compared to the normal ones, suggesting changes in the DNA methylation of these UCNEs may be associated with the development of SCC.
  • Fascinatingly, the level of methylation increased progressively from the healthy samples to the stomatitis samples and then the SCC samples, suggesting a potential role in the progression of the disease.

Conclusion

  • The findings suggest that a hypermethylation pattern in UCNEs may be a common feature of SCC across multiple mammalian species.
  • This implies these particular DNA sequences, and changes in their methylation patterns, could be crucial in understanding and treating this type of skin cancer.

Cite This Article

APA
Morandi L, Sabattini S, Renzi A, Rigillo A, Bettini G, Dervas E, Schauer A, Morandi M, Gissi DB, Tarsitano A, Evangelisti S, Tonon C. (2020). An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species. Cells, 9(9), 2092. https://doi.org/10.3390/cells9092092

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 9
Issue: 9
PII: 2092

Researcher Affiliations

Morandi, Luca
  • Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
Sabattini, Silvia
  • Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
Renzi, Andrea
  • Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
Rigillo, Antonella
  • Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
Bettini, Giuliano
  • Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
Dervas, Eva
  • Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Schauer, Alexandria
  • Institute of Veterinary Pathology, Vetsuisse Faculty, University of Bern, 8466 Bern, Switzerland.
Morandi, Marco
  • Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
Gissi, Davide B
  • Section of Oral Science, Department of Biomedical and Neuromuscular Sciences, University of Bologna, 40125 Bologna, Italy.
Tarsitano, Achille
  • Unit of Oral and Maxillofacial Surgery, Azienda Ospedaliero-Universitaria di Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40138 Bologna, Italy.
Evangelisti, Stefania
  • Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
Tonon, Caterina
  • Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
  • IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità di Neuroimmagini Funzionali e Molecolari, Ospedale Bellaria, 40139 Bologna, Italy.

MeSH Terms

  • Aged
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / veterinary
  • Cats
  • Cattle
  • Conserved Sequence / genetics
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Dogs
  • Epigenesis, Genetic
  • Evolution, Molecular
  • Female
  • Horses / genetics
  • Humans
  • Male
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / veterinary
  • Mustelidae / genetics
  • Porcupines / genetics
  • Prospective Studies
  • Retrospective Studies

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 2 times.
  1. Tresch NS, Fuchs D, Morandi L, Tonon C, Rohrer Bley C, Nytko KJ. Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines. Vet Med Sci 2021 Nov;7(6):2124-2134.
    doi: 10.1002/vms3.620pubmed: 34477324google scholar: lookup
  2. Fuchs D, Rohrer Bley C, Morandi L, Tonon C, Weyland MS, Nytko KJ. Triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro. Vet Med Sci 2023 Jul;9(4):1573-1583.
    doi: 10.1002/vms3.1181pubmed: 37365849google scholar: lookup
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