Circulating Tumor DNA Methylation Biomarkers for Characterization and Determination of the Cancer Origin in Malignant Liver Tumors

SIMPLE SUMMARY: Malignant liver tumors consist of primary tumors and metastases. A correct diagnosis can be achieved with different methods; one of them is the analysis of the cell-free DNA methylation profile in liquid biopsy, which allows for the detection, characterization, and determination of cancer origin. Our review aims to provide an insight into methylation changes in circulating tumor DNA from patients with different malignant liver tumors and may serve as a starting point for further research. ABSTRACT: Malignant liver tumors include primary malignant liver tumors and liver metastases. They are among the most common malignancies worldwide. The disease has a poor prognosis and poor overall survival, especially with liver metastases. Therefore, early detection and differentiation between malignant liver tumors are critical for patient treatment selection. The detection of cancer and the prediction of its origin is possible with a DNA methylation profile of the tumor DNA compared to that of normal cells, which reflects tissue differentiation and malignant transformation. New technologies enable the characterization of the tumor methylome in circulating tumor DNA (ctDNA), providing a variety of new ctDNA methylation biomarkers, which can provide additional information to clinical decision-making. Our review of the literature provides insight into methylation changes in ctDNA from patients with common malignant liver tumors and can serve as a starting point for further research.