DNA methylation profiles in primary cutaneous melanomas are associated with clinically significant pathologic features

Summary 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...

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Bibliographic Details
Published in:Pigment cell and melanoma research 2014-11, Vol.27 (6), p.1097-1105
Main Authors: Thomas, Nancy E., Slater, Nathaniel A., Edmiston, Sharon N., Zhou, Xin, Kuan, Pei-Fen, Groben, Pamela A., Carson, Craig C., Hao, Honglin, Parrish, Eloise, Moschos, Stergios J., Berwick, Marianne, Ollila, David W., Conway, Kathleen
Format: Article
Language:English
Subjects:
Adult
Aged
Cluster Analysis
CpG island methylator phenotype
CpG Islands - genetics
Demography
DNA Methylation - genetics
Female
Genetic Loci
global methylation patterns
Humans
Male
melanoma
Melanoma - genetics
Melanoma - pathology
Melanoma, Cutaneous Malignant
methylation
methylation clusters or subgroups
Middle Aged
Molecular Sequence Data
pathologic features
Phenotype
primary melanoma
Promoter Regions, Genetic
Reproducibility of Results
Skin Neoplasms - genetics
Skin Neoplasms - pathology
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Summary:Summary 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.
ISSN:1755-1471
1755-148X
DOI:10.1111/pcmr.12289