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

Felicity Newell; James S. Wilmott; Peter A. Johansson; Katia Nones; Venkateswar Addala; Pamela Mukhopadhyay; Natasa Broit; Carol M. Amato; Robert Van Gulick; Stephen H. Kazakoff; Ann Marie Patch; Lambros T. Koufariotis; Vanessa Lakis; Conrad Leonard; Scott Wood; Oliver Holmes; Qinying Xu; Karl Lewis; Theresa Medina; Rene Gonzalez; Robyn P.M. Saw; Andrew J. Spillane; Jonathan R. Stretch; Robert V. Rawson; Peter M. Ferguson; Tristan J. Dodds; John F. Thompson; Georgina V. Long; Mitchell P. Levesque; William A. Robinson; John V. Pearson; Graham J. Mann; Richard A. Scolyer; Nicola Waddell; Nicholas K. Hayward

doi:10.1038/s41467-020-18988-3

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

Felicity Newell^*, James S. Wilmott, Peter A. Johansson, Katia Nones, Venkateswar Addala, Pamela Mukhopadhyay, Natasa Broit, Carol M. Amato, Robert Van Gulick, Stephen H. Kazakoff, Ann Marie Patch, Lambros T. Koufariotis, Vanessa Lakis, Conrad Leonard, Scott Wood, Oliver Holmes, Qinying Xu, Karl Lewis, Theresa Medina, Rene GonzalezRobyn P.M. Saw, Andrew J. Spillane, Jonathan R. Stretch, Robert V. Rawson, Peter M. Ferguson, Tristan J. Dodds, John F. Thompson, Georgina V. Long, Mitchell P. Levesque, William A. Robinson, John V. Pearson, Graham J. Mann, Richard A. Scolyer, Nicola Waddell, Nicholas K. Hayward

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	5259
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18988-3
Publication status	Published - 1 Dec 2020

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Newell, F., Wilmott, J. S., Johansson, P. A., Nones, K., Addala, V., Mukhopadhyay, P., Broit, N., Amato, C. M., Van Gulick, R., Kazakoff, S. H., Patch, A. M., Koufariotis, L. T., Lakis, V., Leonard, C., Wood, S., Holmes, O., Xu, Q., Lewis, K., Medina, T., ... Hayward, N. K. (2020). Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity. Nature Communications, 11(1), Article 5259. https://doi.org/10.1038/s41467-020-18988-3

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title = "Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity",

abstract = "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.",

author = "Felicity Newell and Wilmott, {James S.} and Johansson, {Peter A.} and Katia Nones and Venkateswar Addala and Pamela Mukhopadhyay and Natasa Broit and Amato, {Carol M.} and {Van Gulick}, Robert and Kazakoff, {Stephen H.} and Patch, {Ann Marie} and Koufariotis, {Lambros T.} and Vanessa Lakis and Conrad Leonard and Scott Wood and Oliver Holmes and Qinying Xu and Karl Lewis and Theresa Medina and Rene Gonzalez and Saw, {Robyn P.M.} and Spillane, {Andrew J.} and Stretch, {Jonathan R.} and Rawson, {Robert V.} and Ferguson, {Peter M.} and Dodds, {Tristan J.} and Thompson, {John F.} and Long, {Georgina V.} and Levesque, {Mitchell P.} and Robinson, {William A.} and Pearson, {John V.} and Mann, {Graham J.} and Scolyer, {Richard A.} and Nicola Waddell and Hayward, {Nicholas K.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-18988-3",

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Newell, F, Wilmott, JS, Johansson, PA, Nones, K, Addala, V, Mukhopadhyay, P, Broit, N, Amato, CM, Van Gulick, R, Kazakoff, SH, Patch, AM, Koufariotis, LT, Lakis, V, Leonard, C, Wood, S, Holmes, O, Xu, Q, Lewis, K, Medina, T, Gonzalez, R, Saw, RPM, Spillane, AJ, Stretch, JR, Rawson, RV, Ferguson, PM, Dodds, TJ, Thompson, JF, Long, GV, Levesque, MP, Robinson, WA, Pearson, JV, Mann, GJ, Scolyer, RA, Waddell, N & Hayward, NK 2020, 'Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity', Nature Communications, vol. 11, no. 1, 5259. https://doi.org/10.1038/s41467-020-18988-3

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

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5259

ER -

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

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