Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma
The Journal of Pathology, vol. 259, pp. 56–68
Abstract
Melanoma is a heterogenous 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 American Joint Committee on Cancer 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 interferon regulatory factor 4 (IRF4) as a melanoma-associated dependency. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Authors 17
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Affiliation as printed
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Affiliation as printed
Division of Haematology and Immunology University of Leeds School of Medicine Leeds UK
Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK
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Universidade de São Paulo · Wellcome Sanger Institute
Affiliation as printed
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Affiliation as printed
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Affiliation as printed
Division of Haematology and Immunology University of Leeds School of Medicine Leeds UK
Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK
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Affiliation as printed
The Francis Crick Institute London UK
The Francis Crick Institute, London, UK
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Affiliation as printed
Division of Haematology and Immunology University of Leeds School of Medicine Leeds UK
Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK
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Affiliation as printed
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Wellcome Sanger Institute · Universidad Nacional Autónoma de México
Affiliation as printed
Laboratorio Internacional de Investigación sobre el Genoma Humano Universidad Nacional Autónoma de México, Campus Juriquilla Santiago de Querétaro Mexico
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Affiliation as printed
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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Affiliation as printed
The Francis Crick Institute London UK
The Francis Crick Institute, London, UK
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Marieke L. Kuijjer Aachen Department of Pathology and Leiden Center for Computational Oncology Leiden University Medical Center Leiden the Netherlands Department of Pathology and Leiden Center for Computational Oncology
University of Oslo · Leiden University Medical Center
Affiliation as printed
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine University of Oslo Oslo Norway
Department of Pathology and Leiden Center for Computational Oncology Leiden University Medical Center Leiden the Netherlands
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, University of Oslo, Oslo, Norway
Department of Pathology and Leiden Center for Computational Oncology, Leiden University Medical Center, Leiden, the Netherlands
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Instituto Nacional de Câncer - INCA
Affiliation as printed
Division of Experimental and Translational Research Brazilian National Cancer Institute Rio de Janeiro Brazil
Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro, Brazil
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Affiliation as printed
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences University of Sao Paulo Sao Paulo Brazil
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil
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Affiliation as printed
Division of Haematology and Immunology University of Leeds School of Medicine Leeds UK
Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK
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Affiliation as printed
Division of Haematology and Immunology University of Leeds School of Medicine Leeds UK
Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK
Equal contributions
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David J. Adams corresponding
Affiliation as printed
Wellcome Sanger Institute Wellcome Trust Genome Campus Cambridge UK
Equal contributions
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
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