DNA methylation is an independent prognostic marker of survival in adrenocortical cancer

Anne Jouinot, Guillaume Assie, Rossella Libe, Martin Fassnacht, Thomas Papathomas, Olivia Barreau, Bruno De La Villeon, Simon Faillot, Nadim Hamzaoui, Mario Neou, Karine Perlemoine, Fernande Rene-Corail, Stephanie Rodriguez, Mathilde Sibony, Frederique Tissier, Bertrand Dousset, Silviu Sbiera, Cristina Ronchi, Matthias Kroiss, Esther KorpershoekRonald De Krijger, Jens Waldmann, Detlef K. Bartsch, Marcus Quinkler, Magalie Haissaguerre, Antoine Tabarin, Olivier Chabre, Nathalie Sturm, Michaela Luconi, Franco Mantero, Massimo Mannelli, Regis Cohen, Veronique Kerlan, Philippe Touraine, Gaelle Barrande, Lionel Groussin, Xavier Bertagna, Eric Baudin, Laurence Amar, Felix Beuschlein, Eric Clauser, Joel Coste, Jerome Bertherat

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

57 Citations (Scopus)

Résumé

Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. Design: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Setting: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. Patients: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). Main Outcome Measures: DFS and OS. Results: In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P , 0.0001) and OS (P , 0.0001). Methylation, Ki67, and ENSAT stage were combined inmultivariatemodels. For DFS,methylation (P = 0.0005) and stage (P,0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P , 0.0001), and Ki67 (P = 0.024) were independent prognostic factors. Conclusions: Tumor DNA methylation emerges as an independent prognostic factor in ACC. MSMLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.

langue originaleAnglais
Pages (de - à)923-932
Nombre de pages10
journalJournal of Clinical Endocrinology and Metabolism
Volume102
Numéro de publication3
Les DOIs
étatPublié - 1 mars 2017
Modification externeOui

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