DNA methylation is an independent prognostic marker of survival in adrenocortical cancer - Université de Bretagne Occidentale Access content directly
Journal Articles Journal of Clinical Endocrinology and Metabolism Year : 2016

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

Martin Fassnacht
Thomas Papathomas
  • Function : Author
Matthias Kroiss
Jens Waldmann
  • Function : Author
Detlef Bartsch
  • Function : Author
Marcus Quinkler
Antoine Tabarin
  • Function : Author
  • PersonId : 944557
Michaela Luconi
  • Function : Author
Franco Mantero
  • Function : Author
Massimo Mannelli
  • Function : Author
Regis Cohen
  • Function : Author
  • PersonId : 1018684
Philippe Touraine
  • Function : Author
  • PersonId : 983154
Éric Baudin
  • Function : Author
  • PersonId : 957572
Laurence Amar
Felix Beuschlein

Abstract

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 in multivariate models. 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. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.

Dates and versions

hal-02049555 , version 1 (26-02-2019)

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Anne Jouinot, Guillaume Assie, Rossella Libé, Martin Fassnacht, Thomas Papathomas, et al.. DNA methylation is an independent prognostic marker of survival in adrenocortical cancer. Journal of Clinical Endocrinology and Metabolism, 2016, pp.jc.2016-3205. ⟨10.1210/jc.2016-3205⟩. ⟨hal-02049555⟩
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