Human nevi: no longer precursors of melanomas?

Considerable data support the idea that oncogene-induced senescence remains a barrier that needs to be overcome for malignant transformation of melanocytes. Human nevi stain positive for the senescence-associated β-galactosidase marker, suggesting that cells have lost their proliferative capacity. Most nevi harbor B-RAF or N-RAS mutations, implying that they are growth arrested via oncogene-induced senescence pathways. It remains intriguing how benign nevus cells can escape oncogene-induced senescence for malignant transformation to melanoma. The report by Tran et al. in this issue shows that current senescence markers do not distinguish nevi from melanomas, challenging the notion that nevi are growth-arrested via senescence.