Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes-Reference-Cited by-同舟云学术

Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes

Published:2022-09-13 Issue:12 Volume:12 Page:2856-2879
ISSN:2159-8274
Container-title:Cancer Discovery
language:en
Short-container-title:

Author:

Newell Felicity¹^ORCID,Johansson Peter A.¹^ORCID,Wilmott James S.²³⁴^ORCID,Nones Katia¹^ORCID,Lakis Vanessa¹^ORCID,Pritchard Antonia L.¹⁵^ORCID,Lo Serigne N.²^ORCID,Rawson Robert V.²³⁶^ORCID,Kazakoff Stephen H.¹^ORCID,Colebatch Andrew J.²⁶^ORCID,Koufariotis Lambros T.¹^ORCID,Ferguson Peter M.²³⁶^ORCID,Wood Scott¹^ORCID,Leonard Conrad¹^ORCID,Law Matthew H.¹⁷^ORCID,Brooks Kelly M.¹^ORCID,Broit Natasa¹⁸⁹^ORCID,Palmer Jane M.¹^ORCID,Couts Kasey L.¹⁰^ORCID,Vergara Ismael A.²³⁴^ORCID,Long Georgina V.²³⁴¹¹¹²^ORCID,Barbour Andrew P.¹³^ORCID,Nieweg Omgo E.²³^ORCID,Shivalingam Brindha²³¹¹¹⁴¹⁵^ORCID,Robinson William A.¹⁰^ORCID,Stretch Jonathan R.²¹¹¹⁶^ORCID,Spillane Andrew J.²³¹¹¹²^ORCID,Saw Robyn P.M.²³¹¹¹⁶^ORCID,Shannon Kerwin F.²³¹⁶^ORCID,Thompson John F.²³¹¹¹⁶^ORCID,Mann Graham J.²¹⁷¹⁸^ORCID,Pearson John V.¹^ORCID,Scolyer Richard A.²³⁴⁶^ORCID,Waddell Nicola¹^ORCID,Hayward Nicholas K.¹^ORCID

Affiliation:

1. 1QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

2. 2Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.

3. 3Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

4. 4Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

5. 5Department of Genetics and Immunology, Division of Biomedical Science, University of the Highlands and Islands, Inverness, Scotland, United Kingdom.

6. 6Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia.

7. 7Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.

8. 8Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

9. 9Q-Gen Cell Therapeutics, Brisbane, Queensland, Australia.

10. 10Center for Rare Melanomas, University of Colorado Cancer Center, Aurora, Colorado.

11. 11Mater Hospital, North Sydney, New South Wales, Australia.

12. 12Royal North Shore Hospital, St Leonards, New South Wales, Australia.

13. 13Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.

14. 14Department of Neurosurgery, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.

15. 15Department of Neurosurgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

16. 16Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

17. 17Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia.

18. 18John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.

Abstract

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 occurs in internal mucous membranes; and acral melanoma occurs 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 RNA sequencing 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. Significance: This is the largest whole-genome analysis of melanoma to date, comprehensively comparing the genomics of the four major melanoma subtypes. This study highlights both similarities and differences between the subtypes, providing insights into the etiology and biology of melanoma. This article is highlighted in the In This Issue feature, p. 2711

Funder

National Health and Medical Research Council

Melanoma Institute Australia

Melanoma Research Alliance

University of Sydney

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology

Link

https://aacrjournals.org/cancerdiscovery/article-pdf/doi/10.1158/2159-8290.CD-22-0603/3207216/cd-22-0603.pdf

Reference118 articles.