Association of HERV-K and LINE-1 Hypomethylation with Reduced Disease-Free Survival in Melanoma Patients

Abstract

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.

Graphical abstract

In biological samples of primary melanoma (B and C), a decreased methylation level is observed in comparison with melanocyte nevi (A) in human endogenous retrovirus K long terminal repeats and in long interspersed nuclear elements 1 genomic elements. Among melanoma samples of comparable stage and clinical features (B and C), those with lower methylation of human endogenous retrovirus K long terminal repeat (C) have an increased risk of metastases during the follow-up.

Keywords: :

• aging
• disease-free survival
• DNA methylation
• HERV-K
• HML-2
• LINE-1
• melanoma
• prognosis
• retrovirus
• transposon

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0127

Financial & competing interest disclosure

As part of the European TRANSCAN project (JTC2013) “GENMEL” (Identification of genetic markers involved in development of metastases and second cancers in melanoma), this work was supported by the following grant: Italian Ministry of Health, TRANSCAN (JTC2013) - RRC-2015-2360467. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. Informed consent has been obtained from the participants involved.

Additional information

Funding

As part of the European TRANSCAN project (JTC2013) “GENMEL” (Identification of genetic markers involved in development of metastases and second cancers in melanoma), this work was supported by the following grant: Italian Ministry of Health, TRANSCAN (JTC2013) - RRC-2015-2360467. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.