title: DNA methylation profiles in primary cutaneous melanomas are associated with clinically significant pathologic features.
abstract: DNA methylation studies have elucidated a methylation signature distinguishing primary melanomas from benign nevi and provided new insights about genes that may be important in melanoma development. However, it is unclear whether methylation differences among primary melanomas are related to tumor pathologic features with known clinical significance. We utilized the Illumina GoldenGate Cancer Panel array to investigate the methylation profiles of 47 primary cutaneous melanomas. Arraywide methylation patterns revealed a positive association of methylation with Breslow thickness and mutated BRAF, a negative association with mitotic rate, and a weak association with ulceration. Hierarchical clustering on CpG sites exhibiting the most variable methylation (n = 235) divided the melanoma samples into three clusters, including a highly methylated cluster that was positively associated with Breslow thickness and an intermediately methylated cluster associated with Breslow thickness and mitotic rate. Our findings provide support for the existence of methylation-defined subsets in melanomas with increased methylation associated with Breslow thickness.
authors.affiliation: Department of Dermatology, University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Slater
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Edmiston
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Kuan
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Groben
authors.forename: Craig C
authors.initials: CC
authors.lastname: Carson
authors.forename: Honglin
authors.initials: H
authors.lastname: Hao
authors.forename: Eloise
authors.initials: E
authors.lastname: Parrish
authors.forename: Stergios J
authors.initials: SJ
authors.lastname: Moschos
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
authors.forename: David W
authors.initials: DW
authors.lastname: Ollila
authors.forename: Kathleen
authors.initials: K
authors.lastname: Conway
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
keywords: CpG island methylator phenotype; global methylation patterns; melanoma; methylation; methylation clusters or subgroups; pathologic features; primary melanoma