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Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

Lookup NU author(s): Dr Jérémie Nsengimana

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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