Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanomaMore about Open Access at the Crick
Authors listSofia Birkeälv Mark Harland Larissa Satiko Alcântara Sekimoto Matsuyama Mamun Rashid Ishan Mehta Jonathan P Laye Kerstin Haase Tracey Mell Vivek Iyer Carla Daniela Robles-Espinoza Ultan McDermott Peter Van Loo Marieke L Kuijjer Patricia A Possik Silvya Stuchi Maria Engler D Timothy Bishop Julia Newton-Bishop David J Adams
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. This article is protected by copyright. All rights reserved.
Journal Journal of Pathology
Issue number 1