TY - JOUR
T1 - Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity
AU - Newell, Felicity
AU - Wilmott, James S.
AU - Johansson, Peter A.
AU - Nones, Katia
AU - Addala, Venkateswar
AU - Mukhopadhyay, Pamela
AU - Broit, Natasa
AU - Amato, Carol M.
AU - Van Gulick, Robert
AU - Kazakoff, Stephen H.
AU - Patch, Ann Marie
AU - Koufariotis, Lambros T.
AU - Lakis, Vanessa
AU - Leonard, Conrad
AU - Wood, Scott
AU - Holmes, Oliver
AU - Xu, Qinying
AU - Lewis, Karl
AU - Medina, Theresa
AU - Gonzalez, Rene
AU - Saw, Robyn P.M.
AU - Spillane, Andrew J.
AU - Stretch, Jonathan R.
AU - Rawson, Robert V.
AU - Ferguson, Peter M.
AU - Dodds, Tristan J.
AU - Thompson, John F.
AU - Long, Georgina V.
AU - Levesque, Mitchell P.
AU - Robinson, William A.
AU - Pearson, John V.
AU - Mann, Graham J.
AU - Scolyer, Richard A.
AU - Waddell, Nicola
AU - Hayward, Nicholas K.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85092668888&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18988-3
DO - 10.1038/s41467-020-18988-3
M3 - Article
C2 - 33067454
AN - SCOPUS:85092668888
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5259
ER -