Titre
A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Xie, T.
Auteure/Auteur
D' Ario, G.
Auteure/Auteur
Lamb, J.R.
Auteure/Auteur
Martin, E.
Auteure/Auteur
Wang, K.
Auteure/Auteur
Tejpar, S.
Auteure/Auteur
Delorenzi, M.
Auteure/Auteur
Bosman, F.T.
Auteure/Auteur
Roth, A.D.
Auteure/Auteur
Yan, P.
Auteure/Auteur
Bougel, S.
Auteure/Auteur
Di Narzo, A.F.
Auteure/Auteur
Popovici, V.
Auteure/Auteur
Budinská, E.
Auteure/Auteur
Mao, M.
Auteure/Auteur
Weinrich, S.L.
Auteure/Auteur
Rejto, P.A.
Auteure/Auteur
Hodgson, J.G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1932-6203
Statut éditorial
Publié
Date de publication
2012
Volume
7
Numéro
7
Première page
e42001
Peer-reviewed
Oui
Langue
anglais
Résumé
To develop a comprehensive overview of copy number aberrations (CNAs) in stage-II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.8%), 8 q (33.1%) and 13 q (51.0%) and losses on 18 (58.6%), 4 q (26%) and 21 q (21.6%). MSS tumors have significantly more CNAs than microsatellite-instable (MSI) tumors: within the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was identified (p<0.01). Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, and gene expression was highly concordant with copy number aberration for these genes. Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also showed high concordance between copy number and expression. Survival analysis associated a specific patient segment featured by chromosome 20 q gains to an improved overall survival, which might be due to higher expression of genes such as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a poor prognosis BRAF-mutant-like signature derived from mRNA data from this cohort. We further revealed non-random correlation between CNAs among unlinked loci, including positive correlation between 20 q gain and 8 q gain, and 20 q gain and chromosome 18 loss, consistent with co-selection of these CNAs. These results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and highlight loci and genes that may play an important role in driving the development and outcome of this disease.
PID Serval
serval:BIB_2BA5DE2CC521
PMID
Open Access
Oui
Date de création
2012-08-06T12:36:27.943Z
Date de création dans IRIS
2025-05-20T19:41:09Z
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Nom
BIB_2BA5DE2CC521.P001.pdf
Version du manuscrit
published
Taille
1.16 MB
Format
Adobe PDF
PID Serval
serval:BIB_2BA5DE2CC521.P001
URN
urn:nbn:ch:serval-BIB_2BA5DE2CC5216
Somme de contrôle
(MD5):83226de08c715bce29c34efc2947db81