Network-guided analysis of genes with altered somatic copy number and gene expression reveals pathways commonly perturbed in metastatic melanoma.

Détails

Ressource 1Télécharger: BIB_5E0D3CDAAC7D.P001.pdf (419.39 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_5E0D3CDAAC7D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Network-guided analysis of genes with altered somatic copy number and gene expression reveals pathways commonly perturbed in metastatic melanoma.
Périodique
PLoS One
Auteur(s)
Valsesia A., Rimoldi D., Martinet D., Ibberson M., Benaglio P., Quadroni M., Waridel P., Gaillard M., Pidoux M., Rapin B., Rivolta C., Xenarios I., Simpson A.J., Antonarakis S.E., Beckmann J.S., Jongeneel C.V., Iseli C., Stevenson B.J.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
6
Numéro
4
Pages
e18369
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression ('SCNA-genes') in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer.
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/05/2011 8:19
Dernière modification de la notice
20/08/2019 14:16
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