학술논문
Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma.
Document Type
Academic Journal
Author
Birkeälv S; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; Harland M; Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK.; Matsuyama LSAS; 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.; Rashid M; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; Mehta I; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; Laye JP; Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK.; Haase K; The Francis Crick Institute, London, UK.; Mell T; Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK.; Iyer V; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; Robles-Espinoza CD; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Santiago de Querétaro, Mexico.; McDermott U; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.; van Loo P; The Francis Crick Institute, London, UK.; Kuijjer ML; 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.; Possik PA; Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.; Maria Engler SS; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.; Bishop DT; Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK.; Newton-Bishop J; Division of Haematology and Immunology, University of Leeds School of Medicine, Leeds, UK.; Adams DJ; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Source
Publisher: John Wiley And Sons Country of Publication: England NLM ID: 0204634 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-9896 (Electronic) Linking ISSN: 00223417 NLM ISO Abbreviation: J Pathol Subsets: MEDLINE
Subject
Language
English
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.
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
(© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)