Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis
(2018) In Molecular Oncology 12(2). p.239-255- Abstract
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... (More)
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.
(Less)
- author
- Del Castillo Velasco-Herrera, Martin ; van der Weyden, Louise ; Nsengimana, Jeremie ; Speak, Anneliese O. ; Sjöberg, Marcela K. ; Bishop, David Timothy ; Jönsson, Göran LU ; Newton-Bishop, Julia and Adams, David J.
- organization
- publishing date
- 2018-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Comparative genomics, CRISPR, Melanoma, RNA-Seq
- in
- Molecular Oncology
- volume
- 12
- issue
- 2
- pages
- 239 - 255
- publisher
- Elsevier
- external identifiers
-
- pmid:29193607
- scopus:85040030469
- ISSN
- 1574-7891
- DOI
- 10.1002/1878-0261.12161
- language
- English
- LU publication?
- yes
- id
- 9ec700fd-16e3-49ca-b677-ed12b4746c19
- date added to LUP
- 2018-01-15 09:47:18
- date last changed
- 2024-03-31 23:20:14
@article{9ec700fd-16e3-49ca-b677-ed12b4746c19,
abstract = {{<p>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.</p>}},
author = {{Del Castillo Velasco-Herrera, Martin and van der Weyden, Louise and Nsengimana, Jeremie and Speak, Anneliese O. and Sjöberg, Marcela K. and Bishop, David Timothy and Jönsson, Göran and Newton-Bishop, Julia and Adams, David J.}},
issn = {{1574-7891}},
keywords = {{Comparative genomics; CRISPR; Melanoma; RNA-Seq}},
language = {{eng}},
number = {{2}},
pages = {{239--255}},
publisher = {{Elsevier}},
series = {{Molecular Oncology}},
title = {{Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis}},
url = {{http://dx.doi.org/10.1002/1878-0261.12161}},
doi = {{10.1002/1878-0261.12161}},
volume = {{12}},
year = {{2018}},
}