The Francis Crick Institute
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.

Download (8.74 MB)
journal contribution
posted 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)