Comparative genomics provides etiological and biological insights into melanoma subtypes

Felicity Newell, Peter A Johansson, James S Wilmott, Katia Nones, Vanessa Lakis, Antonia L Pritchard, Serigne N Lo, Robert V Rawson, Stephen H Kazakoff, Andrew J Colebatch, Lambros T Koufariotis, Peter M Ferguson, Scott Wood, Conrad Leonard, Matthew H Law, Kelly M Brooks, Natasa Broit, Jane M Palmer, Kasey L Couts, Ismael A VergaraGeorgina V Long, Andrew P Barbour, Omgo E Nieweg, Brindha Shivalingam, William A Robinson, Jonathan R Stretch, Andrew J Spillane, Robyn P M Saw, Kerwin F Shannon, John F Thompson, Graham J Mann, John V Pearson, Richard A Scolyer, Nicola Waddell, Nicholas K Hayward

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
129 Downloads (Pure)


Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation, uveal melanoma occurs in the eyes, mucosal melanoma in internal mucous membranes, and acral melanoma on the palms, soles and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNAseq for subsets of tumors. Uveal melanoma is genomically distinct from other melanoma subtypes, harboring the lowest tumor mutation burden and with significantly mutated genes in the G-protein signaling pathway. Most cutaneous, acral and mucosal melanomas share alterations in components of the MAPK, PI3K, p53, p16 and telomere pathways. However, the mechanism by which these pathways are activated or inactivated varies between melanoma subtypes. Additionally, we identify potential novel germline predisposition genes for some of the less common melanoma subtypes.

Original languageEnglish
Pages (from-to)1-24
Number of pages24
JournalCancer discovery
VolumeDEC 2022
Early online date13 Sept 2022
Publication statusPublished - 1 Nov 2022


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