The Journal of Pathology - 2022 - Birke lv - Mutually exclusive genetic interactions and gene essentiality shape the.pdf (8.74 MB)
Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma.
journal contributionposted on 2022-12-15, 10:29 authored by Sofia 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.
Crick (Grant ID: 10202, Grant title: Van Loo FC001202)