Dataset Information

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.

SUBMITTER: Thomas NE

PROVIDER: S-EPMC4211983 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Thomas Nancy E NE Slater Nathaniel A NA Edmiston Sharon N SN Zhou Xin X Kuan Pei-Fen PF Groben Pamela A PA Carson Craig C CC Hao Honglin H Parrish Eloise E Moschos Stergios J SJ Berwick Marianne M Ollila David W DW Conway Kathleen K

Pigment cell & melanoma research 20140714 6

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 methyla ...[more]

PMID: 24986547

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Project description:BackgroundPrevention of unnecessary biopsies and overtreatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) diseases are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biopsy, for their utility to guide decision making for diagnostic biopsy and early detection of aggressive prostate cancer.ResultsWe recruited 408 patients in risk categories ranging from benign to low-, intermediate-, and high-risk prostate cancer from three international cohorts. Patients were separated into 2/3 training and 1/3 validation cohorts. Methylation biomarkers were analyzed in post-digital rectal exam urinary sediment DNA by quantitative MethyLight assay and investigated for their association with any or aggressive prostate cancers. We developed a Prostate Cancer Urinary Epigenetic (ProCUrE) assay based on an optimal two-gene (HOXD3 and GSTP1) LASSO model, derived from methylation values in the training cohort, and assessed ProCUrE's diagnostic and prognostic ability for prostate cancer in both the training and validation cohorts. ProCUrE demonstrated improved prostate cancer diagnosis and identification of patients with clinically significant disease in both the training and validation cohorts. Using three different risk stratification criteria (Gleason score, D'Amico criteria, and CAPRA score), we found that the positive predictive value for ProCUrE was higher (59.4-78%) than prostate specific antigen (PSA) (38.2-72.1%) for all risk category comparisons. ProCUrE also demonstrated additive value to PSA in identifying GS ??7 PCa compared to PSA alone (DeLong's test p?= 0.039), as well as additive value to the PCPT risk calculator for identifying any PCa and GS ??7 PCa (DeLong's test p?=?0.011 and 0.022, respectively).ConclusionsProCUrE is a promising non-invasive urinary methylation assay for the early detection and prognostication of prostate cancer. ProCUrE has the potential to supplement PSA testing to identify patients with clinically significant prostate cancer.

Dataset Information

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

Publications

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

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