EZH2 alterations in follicular lymphoma: biological and clinical correlations

Abstract : The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n = 55) and H3K27 methylation (n = 63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n = 46, gain n = 23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36–0.93, P = 0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies.
Type de document :
Article dans une revue
Blood Cancer Journal, Nature Publishing Group, 2017, 7 (4), 〈10.1038/bcj.2017.32〉
Liste complète des métadonnées

Littérature citée [37 références]  Voir  Masquer  Télécharger

https://hal.inria.fr/hal-01566524
Contributeur : Marie-France Sagot <>
Soumis le : mercredi 12 juillet 2017 - 11:15:36
Dernière modification le : mardi 29 août 2017 - 16:16:55

Fichier

huet2017.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Sarah Huet, Luc Xerri, Bruno Tesson, Sylvain Mareschal, Sébastien Taix, et al.. EZH2 alterations in follicular lymphoma: biological and clinical correlations. Blood Cancer Journal, Nature Publishing Group, 2017, 7 (4), 〈10.1038/bcj.2017.32〉. 〈hal-01566524v2〉

Partager

Métriques

Consultations de la notice

230

Téléchargements de fichiers

92