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Melanoma Res. 2015 Apr;25(2):173-7. doi: 10.1097/CMR.0000000000000141.

LINE-1 hypermethylation in peripheral blood of cutaneous melanoma patients is associated with metastasis.

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aInternational Research Center bDepartment of Oncogenetics cSkin Cancer Department, A. C. Camargo Cancer Center dDepartment of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo eFederal Technological University of Paraná, Paraná, Brazil.


Aberrant DNA methylation pattern is a well-known epigenetic marker of cancer cells. Recently, aberrant methylation was also reported in the peripheral blood of cancer patients and it could potentially serve as a biomarker for cancer risk. We investigated the methylation pattern of LINE-1 and other repetitive DNA elements in peripheral blood of cutaneous melanoma patients in order to search for an association with clinical characteristics. The patient cohort was composed by 69 unrelated melanoma patients, 28 of whom were hereditary cases (with or without CDKN2A mutations) and 41 were isolated (sporadic) melanoma cases. Methylation of LINE-1 was evaluated by pyrosequencing, whereas additional repetitive DNA sequences were assessed using Illumina 450K methylation microarray. Melanoma patients exhibited a higher, albeit heterogeneous, LINE-1 methylation level compared with controls. Hereditary melanoma patients carrying CDKN2A mutations showed a hypermethylated pattern of both LINE-1 and repetitive DNA elements compared with other patients. In particular, the methylation level at one specific CpG of LINE-1 was found to be correlated with the occurrence of metastasis. Our data suggest that LINE-1 hypermethylation in peripheral blood of melanoma patients is a potential epigenetic biomarker for metastasis occurrence.

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