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Regions of Focal DNA Hypermethylation and Long-Range Hypomethylation in Colorectal Cancer Coincide with Nuclear Lamina-Associated Domains

ABSTRACT: Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor suppressor genes. Genome-scale studies have yielded important insights into these changes, but have focused on CpG islands or gene promoters. We used whole-genome bisulfite sequencing (Bisulfite-Seq) to comprehensively profile a primary human colorectal tumor and adjacent-normal colon tissue at single-basepair resolution. Regions of focal hypermethylation in the tumor were located primarily at CpG islands and were concentrated within regions of long-range (>100 kb) hypomethylation. These hypomethylated domains covered nearly half the genome and coincided with late replication and attachment to the nuclear lamina in human cell lines. The confluence of hypermethylation and hypomethylation within these domains was confirmed in 25 diverse colorectal tumors with matched adjacent tissue. We propose that widespread DNA methylation changes in cancer are linked to silencing programs orchestrated by the 3D organization of chromatin within the nucleus. dbGAP study: phs000385

ORGANISM(S): Homo sapiens

PROVIDER: GSE32399 | GEO | 2011/09/27

SECONDARY ACCESSION(S): PRJNA147931

REPOSITORIES: GEO

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Regions of Focal DNA Hypermethylation and Long-Range Hypomethylation in Colorectal Cancer Coincide with Nuclear Lamina-Associated Domains

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