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Cellular Oncology

, Volume 41, Issue 6, pp 693–698 | Cite as

Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? - a short report

  • Rajesh C. RaoEmail author
  • May P. Chan
  • Chris A. Andrews
  • Alon KahanaEmail author
Report

Abstract

Background

Advanced basal cell carcinomas (BCCs) suffer from a scarcity of effective treatment options. Previously, we found that the targetable histone methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting that epigenetics may play a role in BCC progression. The purpose of this study was to determine whether EZH2-associated proteins and marks may be employed for the stratification of BCC histologic subtypes.

Methods

Sixty-two specimens (from 61 patients), representing more or less aggressive BCC histologic subtypes and matching non-malignant epidermal cells, were included in this study. Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to assess their putative associations with BCC histologic subtypes, as well as with EZH2 and Ki67 expression levels.

Results

We found that H3K27me3 and 5hmC upregulation was positively correlated with the occurrence of a less aggressive BCC histology. The modifications were also positively correlated with each other. Interestingly, we found that they were negatively correlated with the expression of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF, H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non-malignant epidermal cells.

Conclusions

Our data reveal an EZH2-associated epigenetic marker profile that correlates with histologic signs of BCC aggressiveness. Our findings may have diagnostic and therapeutic implications, and indicate that epigenetic markers may be shared even with relatively less aggressive tumor types, thereby suggesting universal themes.

Keywords

Epigenetics Histone methyltransferase Histone acetyltransferase Skin cancer Basal cell carcinoma Biomarkers 

Notes

Acknowledgements

Supported in part by the National Institutes of Health (P30CA046592) VISORB clinical trial (ClinicalTrials.gov Identifier: NCT02436408; A.K. principal investigator) with support from Genentech, Inc. A.K. is supported by the Forbes Cancer Research Institute and the A. Alfred Taubman Medical Research Institute. A.K. is recipient of a Clinician-Scientist Award from Research to Prevent Blindness (RPB), and R.C.R. is a recipient of an RPB Career Development Award. R.C.R. is supported by Career Development Awards from the National Institutes of Health (K08EY026654) and the A. Alfred Taubman Medical Research Institute, where he is the Leslie and Abigail Wexner Emerging Scholar. R.C.R. received funding from the Leonard G. Miller Ophthalmic Research Fund at the Kellogg Eye Center, Grossman Research Fund, Barbara Dunn Research Fund, Roz Greenspoon Research Fund, Beatrice & Reymont Paul Foundation and March Hoops to Beat Blindness. The authors acknowledge generous support from an unrestricted research grant from RPB to the Department of Ophthalmology and Visual Sciences at the University of Michigan. None of the sponsors participated in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review or approval of the manuscript; and the decision to submit the manuscript for publication.

Author contribution

R.C.R. and A.K. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Compliance with ethical standards

Conflict of interest

The authors report no other conflicts of interest.

Supplementary material

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Supplemental Table 1 (DOCX 63 kb)
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Supplementary Fig. 1

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High resolution image (TIFF 56036 kb)
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Supplementary Fig. 2

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Copyright information

© International Society for Cellular Oncology 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye CenterUniversity of MichiganAnn ArborUSA
  2. 2.Department of PathologyUniversity of MichiganAnn ArborUSA
  3. 3.Comprehensive Cancer CenterUniversity of MichiganAnn ArborUSA
  4. 4.Section of Ophthalmology, Surgery ServiceVA Ann Arbor Health SystemAnn ArborUSA
  5. 5.Department of DermatologyUniversity of MichiganAnn ArborUSA

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