title: Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network.
abstract: Metastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2, and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles, and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity.
authors.affiliation: Sanford-Burnham Medical Research Institute, Orlando FL 32827 USA.
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Mazar
authors.forename: Cuncong
authors.initials: C
authors.lastname: Zhong
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Faulkner
authors.forename: Subramaniam S
authors.initials: SS
authors.lastname: Govindarajan
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Dinger
authors.forename: Gavin
authors.initials: G
authors.lastname: Meredith
authors.forename: Christopher
authors.initials: C
authors.lastname: Adams
authors.forename: Shaojie
authors.initials: S
authors.lastname: Zhang
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.forename: Animesh
authors.initials: A
authors.lastname: Ray
authors.forename: Ranjan J
authors.initials: RJ
authors.lastname: Perera
mesh_terms: D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid