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Article

Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course

1
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland
2
Department of Tumor Pathology, Greater Poland Cancer Centre, Garbary 15, 61-866 Poznan, Poland
3
Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 84, 60-569 Poznan, Poland
4
Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Pawel Karpinski and Maria M. Sasiadek
Int. J. Mol. Sci. 2022, 23(11), 5962; https://doi.org/10.3390/ijms23115962
Received: 25 April 2022 / Revised: 20 May 2022 / Accepted: 23 May 2022 / Published: 25 May 2022
(This article belongs to the Special Issue Epigenetic Mechanisms and Human Pathology 2.0)
Pleomorphic adenomas (PAs) are the most frequently diagnosed benign salivary gland tumors. Although the majority of PAs are characterized by slow growth, some develop very fast and are more prone to recur. The reason for such differences remains unidentified. In this study, we performed global DNA methylation profiling using the Infinium Human Methylation EPIC 850k BeadChip Array (Illumina) to search for epigenetic biomarkers that could distinguish both groups of tumors. The analysis was performed in four fast-growing tumors (FGTs) and four slow-growing tumors (SGTs). In all, 85 CpG dinucleotides differentiating both groups were identified. Six CpG tags (cg06748470, cg18413218, cg10121788, cg08249296, cg18455472, and cg19930657) were selected for bisulfite pyrosequencing in the extended group of samples. We confirmed differences in DNA methylation between both groups of samples. To evaluate the potential diagnostic accuracy of the selected markers, ROC curves were constructed. We indicated that CpGs included in two assays showed an area under the curve with an acceptable prognostic value (AUC > 0.7). However, logistic regression analysis allowed us to indicate a more optimal model consisting of five CpGs ((1) cg06748470, (2) cg00600454, (3) CpG located in chr14: 77,371,501–77,371,502 (not annotated in GRCh37/hg19), (4) CpG2 located in chr16: 77,469,589–77,469,590 (not annotated GRCh37/hg19), and (5) cg19930657) with AUC > 0.8. This set of epigenetic biomarkers may be considered as differentiating factors between FGT and SGT during salivary gland tumor diagnosis. However, this data should be confirmed in a larger cohort of samples. View Full-Text
Keywords: salivary gland pleomorphic adenoma; fast-growing tumors; slow-growing tumors; DNA methylation; CpG; bisulfite pyrosequencing salivary gland pleomorphic adenoma; fast-growing tumors; slow-growing tumors; DNA methylation; CpG; bisulfite pyrosequencing
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MDPI and ACS Style

Kiwerska, K.; Kowal-Wisniewska, E.; Ustaszewski, A.; Bartkowiak, E.; Jarmuz-Szymczak, M.; Wierzbicka, M.; Giefing, M. Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course. Int. J. Mol. Sci. 2022, 23, 5962. https://doi.org/10.3390/ijms23115962

AMA Style

Kiwerska K, Kowal-Wisniewska E, Ustaszewski A, Bartkowiak E, Jarmuz-Szymczak M, Wierzbicka M, Giefing M. Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course. International Journal of Molecular Sciences. 2022; 23(11):5962. https://doi.org/10.3390/ijms23115962

Chicago/Turabian Style

Kiwerska, Katarzyna, Ewelina Kowal-Wisniewska, Adam Ustaszewski, Ewelina Bartkowiak, Malgorzata Jarmuz-Szymczak, Malgorzata Wierzbicka, and Maciej Giefing. 2022. "Global DNA Methylation Profiling Reveals Differentially Methylated CpGs between Salivary Gland Pleomorphic Adenomas with Distinct Clinical Course" International Journal of Molecular Sciences 23, no. 11: 5962. https://doi.org/10.3390/ijms23115962

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