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Lookup NU author(s): Dr Jérémie Nsengimana
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.Metastasis is the leading cause of death in patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonisation are poorly understood. Here, we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this, we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. Next, we characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and their highly metastatic derivatives. By comparing expression data between species, we identified lunatic fringe (LFNG), among 28 genes whose expression level is predictive of poor prognosis and whose altered expression is associated with a prometastatic phenotype in mouse melanoma cells. CRISPR/Cas9-mediated knockout of Lfng dramatically enhanced the capability of weakly metastatic melanoma cells to metastasise in vivo, a phenotype that could be rescued with the Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using comparative genomics, we show that LFNG expression plays a functional role in regulating melanoma metastasis.
Author(s): Del Castillo Velasco-Herrera M, van der Weyden L, Nsengimana J, Speak AO, Sjoberg MK, Bishop DT, Jonsson G, Newton-Bishop J, Adams DJ
Publication type: Article
Publication status: Published
Journal: Molecular Oncology
Year: 2018
Volume: 12
Issue: 2
Pages: 239-255
Print publication date: 01/02/2018
Online publication date: 29/11/2017
Acceptance date: 07/11/2017
Date deposited: 12/06/2020
ISSN (print): 1574-7891
ISSN (electronic): 1878-0261
Publisher: John Wiley and Sons Ltd.
URL: https://doi.org/10.1002/1878-0261.12161
DOI: 10.1002/1878-0261.12161
PubMed id: 29193607
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