Birkeälv, S, Harland, M, Matsuyama, LSAS et al. (15 more authors) (2023) Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma. Journal of Pathology, 259 (1). pp. 56-68. ISSN 0022-3417
Abstract
Melanoma is a heterogeneous malignancy with an unpredictable clinical course. Most patients who present in the clinic are diagnosed with primary melanoma, yet large-scale sequencing efforts have focused primarily on metastatic disease. In this study we sequence-profiled 524 AJCC Stage I-III primary tumours. Our analysis of these data reveals recurrent driver mutations, mutually exclusive genetic interactions, where two genes were never or rarely co-mutated, and an absence of co-occurring genetic events. Further, we intersected copy number calls from our primary melanoma data with whole-genome CRISPR screening data to identify the transcription factor IRF4 as a melanoma-associated dependency.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Melanoma; gene essentiality; genetic epistasis; genomic landscape; CRISPR screening; IRF4; genome sequencing; somatic mutation; driver genes; primary cancer |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK Supplier No: 138573 c588/A19167 |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 Nov 2022 16:20 |
Last Modified: | 09 Jan 2023 15:01 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/path.6019 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:192797 |