Titre
Identification of a Poor-Prognosis BRAF-Mutant-Like Population of Patients With Colon Cancer.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Popovici, V.
Auteure/Auteur
Budinska, E.
Auteure/Auteur
Tejpar, S.
Auteure/Auteur
Weinrich, S.
Auteure/Auteur
Estrella, H.
Auteure/Auteur
Hodgson, G.
Auteure/Auteur
Van Cutsem, E.
Auteure/Auteur
Xie, T.
Auteure/Auteur
Bosman, F.T.
Auteure/Auteur
Roth, A.D.
Auteure/Auteur
Delorenzi, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1527-7755
Statut éditorial
Publié
Date de publication
2012
Volume
30
Numéro
12
Première page
1288
Dernière page/numéro d’article
1295
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
PURPOSE Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications. Materials and METHODS A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression-based classifier for detecting BRAF mutant samples with high sensitivity. The classifier was validated in independent data sets, and survival rates were compared between classifier positive and negative tumors. Results A 64 gene-based classifier was developed with 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of double wild type) showed a gene expression pattern and had poor overall survival and survival after relapse, similar to those observed in BRAF-mutant patients. Thus they form a distinct prognostic subgroup within their mutation class. CONCLUSION A characteristic pattern of gene expression is associated with and accurately predicts BRAF mutation status and, in addition, identifies a population of BRAF mutated-like KRAS mutants and double wild-type patients with similarly poor prognosis. This suggests a common biology between these tumors and provides a novel classification tool for cancers, adding prognostic and biologic information that is not captured by the mutation status alone. These results may guide therapeutic strategies for this patient segment and may help in population stratification for clinical trials.
PID Serval
serval:BIB_FCB790038FBB
PMID
Date de création
2012-05-28T16:16:54.243Z
Date de création dans IRIS
2025-05-21T06:24:57Z