Key genetic factor keeps moles from becoming melanoma

August 26, 2015

Researchers at the University of Pennsylvania have identified a major genetic factor that keeps moles in their usual non-cancerous, no-growth state. The researchers found that a tumour suppressor protein, p15, is important for holding regular moles in a benign state, and that any subsequent loss of p15 promotes the transition to melanoma.

Abstract

Deletion of the entire CDKN2B-CDKN2A gene cluster is among the most common genetic events in cancer. The tumor-promoting effects are generally attributed to loss of CDKN2A-encoded p16 and p14ARF tumor suppressors. The degree to which the associated CDKN2B-encoded p15 loss contributes to human tumorigenesis is unclear.

Here we show that CDKN2B is highly upregulated in benign melanocytic nevi, contributes to maintaining nevus melanocytes in a growth-arrested premalignant state, and is commonly lost in melanoma. Using primary melanocytes isolated directly from freshly excised human nevi naturally expressing the common BRAF(V600E) activating mutation, nevi progressing to melanoma, and normal melanocytes engineered to inducibly express BRAF(V600E), we show that BRAF activation results in reversible, TGFβ-dependent, p15 induction that halts proliferation. Further, we engineer human skin grafts containing nevus-derived melanocytes to establish a new, architecturally faithful, in vivo melanoma model, and demonstrate that p15 loss promotes the transition from benign nevus to melanoma.

Source:
McNea, AS. CDKN2B loss promotes progression from benign melanocytic nevus to melanoma. Cancer Discovery. Published OnlineFirst July 16, 2015; doi: 10.1158/2159-8290.CD-15-0196 http://cancerdiscovery.aacrjournals.org/content/ea...

See also:
University of Pennsylvania media release: http://www.uphs.upenn.edu/news/News_Releases/2015/...