Recognizing DNA Methylation Patterns and Their Functionality in Merkel Cell Carcinoma
Posted: Tuesday, October 19, 2021
In findings presented in BMC Genome Medicine, investigators demonstrated specific DNA methylation patterns for primary and metastatic Merkel cell carcinomas and adjacent-normal tissue that may improve the management of these cancers. Gangning Liang, MD, PhD, of the Norris Comprehensive Cancer Center at the University of Southern California, Los Angeles, and colleagues also found that these DNA methylation markers tended to correlate with Merkel cell carcinoma tumorigenesis, expression of the Merkel cell polyomavirus (MCPyV), neuroendocrine features, and histone H3 lysine 27 trimethylation (H3K27me3) status.
“Taken together, our identification of Merkel cell carcinoma–specific DNA methylation markers may help provide the foundation for novel methodologies in the clinical diagnosis and prognostication of Merkel cell carcinomas,” the authors concluded. “It should be noted that DNA is especially stable and easy to obtain from patients in the clinical setting, [and] DNA methylation markers are easily detected by various global or locus-specific assays.”
In this trial, the authors collected tumor samples from 11 patients who underwent surgical resection of primary Merkel cell tumors (8 samples), had regional lymph nodes (4 samples), and in-transit skin metastases (3 samples). Adjacent normal tissue from the patients was used as a control.
The authors found that “significant” DNA methylation patterns existed when comparing the four tissue types, as well as when comparing MCPyV status. In total, 964 genes directly regulated by promoter or gene body DNA methylation were identified with high enrichment in neurologically related pathways. The authors noted that this strengthens the possibility that DNA methylation is directly involved in Merkel cell carcinoma tumorigenesis.
Additionally, KDM6B promoter DNA hypomethylation was found to be enriched in MCPyV-positive Merkel cell carcinomas and correlated with KDM6B overexpression. EZHIP promoter DNA hypomethylation and subsequent gene expression were also found in Merkel cell carcinomas—regardless of the sample’s MCPyV status. This suggested, the authors added, that the upregulation of KDM6B and EZHIP may contribute to the global loss of H3K27me3 in cases of Merkel cell carcinoma.
Disclosure: For full disclosures of the study authors, visit biomedcentral.com.
