Dataset Information

DNA methylation characteristics of primary melanomas with distinct biological behaviour.

ABSTRACT: In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAF(V600E) mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations.

SUBMITTER: Ecsedi S

PROVIDER: S-EPMC4022506 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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DNA methylation characteristics of primary melanomas with distinct biological behaviour.

Ecsedi Szilvia S Hernandez-Vargas Hector H Lima Sheila C SC Vizkeleti Laura L Toth Reka R Lazar Viktoria V Koroknai Viktoria V Kiss Timea T Emri Gabriella G Herceg Zdenko Z Adany Roza R Balazs Margit M

PloS one 20140515 5

In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and assoc ...[more]

PMID: 24832207

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Project description:STUDY QUESTION:Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age? SUMMARY ANSWER:Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age. WHAT IS KNOWN ALREADY:A study of 397 young Filipino women (ages 20-22) observed increasing epigenetic age with an increasing number of pregnancies. STUDY DESIGN, SIZE, DURATION:We used data from 2356 non-Hispanic white women (ages 35-74) enrolled in the Sister Study cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS:Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina's HumanMethylation450 BeadChip. We estimated association ?-values and 95% CIs using linear regression. MAIN RESULTS AND THE ROLE OF CHANCE:All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: ? = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: ? = 0.12, 95% CI = -0.04, 0.27, P = 0.14; Levine: ? = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (? = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (? = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P? 1.0 × 10-7). LIMITATIONS, REASONS FOR CAUTION:We relied on retrospective recall to ascertain reproductive history and pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS:Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome. STUDY FUNDING/COMPETING INTEREST(S):This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER:Not applicable.

Dataset Information

DNA methylation characteristics of primary melanomas with distinct biological behaviour.

Publications

DNA methylation characteristics of primary melanomas with distinct biological behaviour.

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