A substantial part of cutaneous malignant melanomas develops from benign nevi. While the mutational landscape of melanoma has been investigated in recent years, the molecular events leading to the malignant transformation remain less characterized. To explore these processes on a proteomic level, we created a cohort of melanomas (N=166) and identified malignant melanomas with a nevi remnant in the same specimen (N=14). We applied a combination of laser microdissection and mass spectrometry based proteomic analysis of nevi melanocytes and melanomas. We quantified 5749 proteins. Differential expression analysis revealed 88 proteins were upregulated and 229 proteins were downregulated in melanoma vs nevi (FDR<0.05, FC>2), including 180 proteins that overlapped with cancer hallmark genes, representing all ten cancer hallmarks. Pathway analyses revealed upregulation of several core components of the Hippo-Yap pathway and PI3K–mTOR pathway in melanoma cells. Furthermore, changes in metabolism, upregulation of cell-cycle associated MCM proteins and CDK2, and downregulation in tumor suppressor PDCD4 were found in melanoma. In conclusion, we report proteomic changes and new drivers in the malignant transformation of nevi to melanoma.

ESDR440 - The Proteome of microdissected nevi- and melanoma cells reveal upregulation of Hippo-YAP and PI3K-mTOR pathway

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.