Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors

摘要: Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation oncogenes the tumorigenic process. However, most these been limited analysis promoters CpG islands (CGIs). Recently, new technologies for whole-genome DNAm (methylome) developed, enabling unbiased methylomes. By using MeDIP-seq, we report a sequencing-based comparative methylome malignant peripheral nerve sheath tumors (MPNSTs), benign neurofibromas, normal Schwann cells. Analysis methylomes revealed complex landscape alterations. In contrast what has reported other types, no significant global observed in MPNSTs by MeDIP-seq. highly (P < 10−100) directional difference found satellite repeats, suggesting repeats be main target MPNSTs. Comparative MPNST cell identified 101,466 cancer-associated differentially methylated regions (cDMRs). showed cDMRs significantly enriched two repeat types (SATR1 ARLα) suggests an association between aberrant sequences transition from healthy cells disease. Significant enrichment hypermethylated CGI shores 10−60), non–CGI-associated 10−4) hypomethylated SINE also identified. Integration gene expression data that pattern with shore able discriminate disease phenotypes. This study establishes MeDIP-seq as effective method analyze