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 Vergara; Georgina 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

doi:10.1158/2159-8290.CD-22-0603

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 journal › Article › peer-review

37 Citations (Scopus)

222 Downloads (Pure)

Abstract

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 language	English
Pages (from-to)	1-24
Number of pages	24
Journal	Cancer discovery
Volume	DEC 2022
Early online date	13 Sept 2022
DOIs	https://doi.org/10.1158/2159-8290.CD-22-0603
Publication status	Published - 1 Nov 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1158/2159-8290.CD-22-0603Licence: CC BY-NC-ND

AAM
©2022 The Authors; Published by the American Association for Cancer Research
Accepted author manuscript, 2.74 MBLicence: CC BY-NC-ND
Comparative Genomics Provides Etiologic
©2022 The Authors; Published by the American Association for Cancer Research This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
Final published version, 28.6 MBLicence: CC BY-NC-ND

Cite this

Newell, F., Johansson, P. A., Wilmott, J. S., Nones, K., Lakis, V., Pritchard, A. L., Lo, S. N., Rawson, R. V., Kazakoff, S. H., Colebatch, A. J., Koufariotis, L. T., Ferguson, P. M., Wood, S., Leonard, C., Law, M. H., Brooks, K. M., Broit, N., Palmer, J. M., Couts, K. L., ... Hayward, N. K. (2022). Comparative genomics provides etiological and biological insights into melanoma subtypes. Cancer discovery, DEC 2022, 1-24. https://doi.org/10.1158/2159-8290.CD-22-0603

@article{43432b3122924e8fa2dd529ded29b171,

title = "Comparative genomics provides etiological and biological insights into melanoma subtypes",

abstract = "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.",

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

year = "2022",

month = nov,

day = "1",

doi = "10.1158/2159-8290.CD-22-0603",

language = "English",

volume = "DEC 2022",

pages = "1--24",

journal = "Cancer discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research Inc.",

}

Newell, F, Johansson, PA, Wilmott, JS, Nones, K, Lakis, V, Pritchard, AL, Lo, SN, Rawson, RV, Kazakoff, SH, Colebatch, AJ, Koufariotis, LT, Ferguson, PM, Wood, S, Leonard, C, Law, MH, Brooks, KM, Broit, N, Palmer, JM, Couts, KL, Vergara, IA, Long, GV, Barbour, AP, Nieweg, OE, Shivalingam, B, Robinson, WA, Stretch, JR, Spillane, AJ, Saw, RPM, Shannon, KF, Thompson, JF, Mann, GJ, Pearson, JV, Scolyer, RA, Waddell, N & Hayward, NK 2022, 'Comparative genomics provides etiological and biological insights into melanoma subtypes', Cancer discovery, vol. DEC 2022, pp. 1-24. https://doi.org/10.1158/2159-8290.CD-22-0603

TY - JOUR

T1 - Comparative genomics provides etiological and biological insights into melanoma subtypes

AU - Newell, Felicity

AU - Johansson, Peter A

AU - Wilmott, James S

AU - Nones, Katia

AU - Lakis, Vanessa

AU - Pritchard, Antonia L

AU - Lo, Serigne N

AU - Rawson, Robert V

AU - Kazakoff, Stephen H

AU - Colebatch, Andrew J

AU - Koufariotis, Lambros T

AU - Ferguson, Peter M

AU - Wood, Scott

AU - Leonard, Conrad

AU - Law, Matthew H

AU - Brooks, Kelly M

AU - Broit, Natasa

AU - Palmer, Jane M

AU - Couts, Kasey L

AU - Vergara, Ismael A

AU - Long, Georgina V

AU - Barbour, Andrew P

AU - Nieweg, Omgo E

AU - Shivalingam, Brindha

AU - Robinson, William A

AU - Stretch, Jonathan R

AU - Spillane, Andrew J

AU - Saw, Robyn P M

AU - Shannon, Kerwin F

AU - Thompson, John F

AU - Mann, Graham J

AU - Pearson, John V

AU - Scolyer, Richard A

AU - Waddell, Nicola

AU - Hayward, Nicholas K

PY - 2022/11/1

Y1 - 2022/11/1

N2 - 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.

AB - 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.

U2 - 10.1158/2159-8290.CD-22-0603

DO - 10.1158/2159-8290.CD-22-0603

M3 - Article

C2 - 36098958

SN - 2159-8274

VL - DEC 2022

SP - 1

EP - 24

JO - Cancer discovery

JF - Cancer discovery

ER -

Comparative genomics provides etiological and biological insights into melanoma subtypes

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this