Highly Aggressive Metastatic Melanoma Cells Unable to Maintain Telomere Length

Abstract

Summary: Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase. Our data further support the emerging idea that long telomeres promote melanoma formation. These observations are important when considering anticancer therapies targeting telomerase. : Viceconte et al. report that metastatic cutaneous melanoma cells display long telomeres and do not always have an active telomere maintenance mechanism, showing that the ability to maintain telomeres is not an absolute requirement for metastasis formation. These observations are important in the context of anti-cancer therapies targeting telomerase. Keywords: telomeres, telomerase, melanoma, ever-shorter telomeres, immortalization