Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

• Published in: Nature communications 2020-10, Vol.11 (1), p.5259-14, Article 5259
• Main Authors: Newell, Felicity, Wilmott, James S., Johansson, Peter A., Nones, Katia, Addala, Venkateswar, Mukhopadhyay, Pamela, Broit, Natasa, Amato, Carol M., Van Gulick, Robert, Kazakoff, Stephen H., Patch, Ann-Marie, Koufariotis, Lambros T., Lakis, Vanessa, Leonard, Conrad, Wood, Scott, Holmes, Oliver, Xu, Qinying, Lewis, Karl, Medina, Theresa, Gonzalez, Rene, Saw, Robyn P. M., Spillane, Andrew J., Stretch, Jonathan R., Rawson, Robert V., Ferguson, Peter M., Dodds, Tristan J., Thompson, John F., Long, Georgina V., Levesque, Mitchell P., Robinson, William A., Pearson, John V., Mann, Graham J., Scolyer, Richard A., Waddell, Nicola, Hayward, Nicholas K.
• Format: Article
• Language: English
• Subjects: 45/23; 45/91; 631/114/2785; 631/208/69; 631/67/1813/1634; Female; Gene Amplification; Gene Dosage; Genomics; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Humanities and Social Sciences; Humans; Male; Melanoma - genetics; Melanoma - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; multidisciplinary; Mutation; Oxidoreductases - genetics; Oxidoreductases - metabolism; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Receptor, Notch2 - genetics; Receptor, Notch2 - metabolism; Science; Science (multidisciplinary); Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Whole Genome Sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18988-3

To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS , NF1 , NOTCH2 , PTEN and TYRP1 . Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT , CDK4 , MDM2 , CCND1 , PAK1 and GAB2 , indicating potential therapeutic options. Acral melanoma occurs on the soles of the feet, palms of the hands and in nail beds. Here, the authors reports the genomic landscape of 87 acral melanomas and find that some tumors harbor a UV signature and that the tumors are diverse at the levels of mutational signatures, structural aberrations and copy number signatures.