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- Title
DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer.
- Authors
Jouinot, Anne; Assie, Guillaume; Libe, Rossella; Fassnacht, Martin; Papathomas, Thomas; Barreau, Olivia; DE LA Villeon, Bruno; Faillot, Simon; Hamzaoui, Nadim; Neou, Mario; Perlemoine, Karine; Rene-Corail, Fernande; Rodriguez, Stéphanie; Sibony, Mathilde; Tissier, Frédérique; Dousset, Bertrand; Sbiera, Silviu; Ronchi, Cristina; Kroiss, Matthias; Korpershoek, Esther
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort.<bold>Design: </bold>Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA).<bold>Setting: </bold>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.<bold>Patients: </bold>The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors).<bold>Main Outcome Measures: </bold>DFS and OS.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2016, pjc20163205
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2016-3205