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Endocrine Abstracts (2012) 29 OC13.4

ICEECE2012 Oral Communications Adrenal Basic (6 abstracts)

A genome-wide methylation study of adrenocortical tumors shows specific alterations linked to gene expression, revealing new aspects of the molecular classification of adrenal carcinomas

G. Assié 1, , O. Barreau 1 , H. Wilmot-Roussel 1, , B. Ragazzon 1 , C. Baudry 1, , K. Perlemoine 1 , F. René-Corail 1 , B. Dousset 1, , X. Bertagna 1, , F. Tissier 1, , A. De Reyniès 4 & J. Bertherat 1,


1Institut Cochin, Paris, France; 2Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France; 3Center for, Paris, France; 4Ligue Nationale Contre Le Cancer, Paris, France.


Introduction: DNA methylation is a mechanism for gene expression dysregulation in cancer. Little is known about methylation in adrenocortical tumors (ACT). Previous transcriptome studies proposed an original classification of ACT, first discriminating carcinomas from adenomas, then separating the carcinomas in two groups with different prognosis (C1A and C1B), the poor outcome group (C1A) being divided in three subgroups: p53 inactivation sub-group (C1Ap53), β-catenin activation sub-group (C1Aβcatenin), and a third with no known molecular alteration (C1Ax). Here we studied the genes promoter methylation, and the relation between methylation and gene expression in ACT, especially with the transcriptome classification of ACT.

Patients and methods: Genome-wide methylation patterns of 84 adenomas and 51 carcinomas were studied by the Infinium HumanMethylation27 Beadchip (Illumina). Gene expression data were available for 87 tumors, including 34 carcinomas (HG-U133Plus2.0 AffymetrixGeneChip, Affymetrix).

Results: Overall, the carcinomas are more methylated than the adenomas (Wilcoxon-test, P=7e-07). Methylation varies among transcriptome-based subgroups of carcinomas: two subgroups of poor outcome harbor a high level of methylation (C1Ap53 and C1Ax), one of poor outcome a low level of methylation (C1Aβcatenin), and one of better outcome an intermediate level of methylation (C1B).

A few genes are recurrently hypermethylated in carcinomas whatever the group (ex: H19), other genes having subgroup-specific methylation. The transcriptome/methylation correlation shows 1741 genes (out of 12 250) negatively correlated; among the top genes are the expected H19 and several tumor suppressors (PLAGL-1, G0S2, NDRG2).

Methylation and expression also show regional patterns, among which are the regions 1q22, 8p21.3, 11p15 and 17p13.1.

Conclusions: This first ACT genome-wide methylation study shows that specific methylation profiles characterize the transcriptome-identified subgroups of carcinomas. It identifies tumor suppressor genes with recurrent methylation aberrations, related to gene expression deregulation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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