Genome-wide promoter methylation profiling in a cellular model of melanoma progression reveals markers of malignancy and metastasis that predict melanoma survival. Academic Article uri icon

Overview

abstract

  • The epigenetic changes associated with melanoma progression to advanced and metastatic stages are still poorly understood. To shed light on the CpG methylation dynamics during melanoma development, we analyzed the methylome profiles of a four-stage cell line model of melanoma progression: non-tumorigenic melanocytes (melan-a), premalignant melanocytes (4C), non-metastatic melanoma cells (4C11-), and metastatic melanoma cells (4C11+). We identified 540 hypo- and 37 hypermethylated gene promoters that together characterized a malignancy signature, and 646 hypo- and 520 hypermethylated promoters that distinguished a metastasis signature. Differentially methylated genes from these signatures were correlated with overall survival using TCGA-SKCM methylation data. Moreover, multivariate Cox analyses with LASSO regularization identified panels of 33 and 31 CpGs, respectively, from the malignancy and metastasis signatures that predicted poor survival. We found a concordant relationship between DNA methylation and transcriptional levels for genes from the malignancy (Pyroxd2 and Ptgfrn) and metastasis (Arnt2, Igfbp4 and Ptprf) signatures, which were both also correlated with melanoma prognosis. Altogether, this study reveals novel CpGs methylation markers associated with malignancy and metastasis that collectively could improve the survival prediction of melanoma patients.

publication date

  • May 23, 2022

Research

keywords

  • DNA Methylation
  • Melanoma

Identity

PubMed Central ID

  • PMC9128240

Scopus Document Identifier

  • 85130686347

Digital Object Identifier (DOI)

  • 10.1093/nar/gkz114

PubMed ID

  • 35606887

Additional Document Info

volume

  • 14

issue

  • 1