Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylation profiling of human adrenocortical tumors (ACTs)

ABSTRACT: A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Transcriptome analysis led to the unsupervised classification of carcinomas in two groups, associated with different outcomes {de Reynies, 2009 ; Giordano, 2009}. Subsequently, we have shown that unsupervised clustering further classified the tumors of the poor prognosis group in three different subgroups, two of them harbouring a cardinal molecular alteration {Ragazzon, 2010}. One is associated with p53 inactivation, the second with ?-catenin activation. No molecular defect has been identified in the third group so far. The aim is to describe the genome-wide methylome of adrenocortical tumors, and to assess the link with previously established molecular classifications. Experimental design: Genome-wide methylation patterns of 84 adenomas and 51 carcinomas were obtained with the Infinium HumanMethylation27 beadchip (Illumina). | Submitter : Olivia Barreau | Project leader : Jerome Bertherat

ORGANISM(S): Homo sapiens

DISEASE(S): Adrenocortical Adenoma

SUBMITTER: Olivia Barreau

PROVIDER: E-MTAB-815 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification of a CpG island methylator phenotype in adrenocortical carcinomas.

Barreau Olivia O Assié Guillaume G Wilmot-Roussel Hortense H Ragazzon Bruno B Baudry Camille C Perlemoine Karine K René-Corail Fernande F Bertagna Xavier X Dousset Bertrand B Hamzaoui Nadim N Tissier Frédérique F de Reynies Aurélien A Bertherat Jérôme J

The Journal of clinical endocrinology and metabolism 20121023 1

<h4>Purpose</h4>DNA methylation is a mechanism for gene expression silencing in cancer. Limited information is available for adrenocortical tumors. Abnormal methylation at the IGF2/H19 locus is common in adrenocortical carcinomas. Our aim was to characterize the methylation in adrenocortical carcinomas at a whole-genome scale and to assess its clinical significance and its impact on gene expression.<h4>Experimental design</h4>Methylation patterns of CpG islands in promoter regions of 51 adrenoco ...[more]

PMID: 23093492

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Project description:Pathologic differentiation of tissue of origin in tumors found in the lung can be challenging, with differentiation of mesothelioma and lung adenocarcinoma emblematic of this problem. Indeed, proper classification is essential for determination of treatment regimen for these diseases, making accurate and early diagnosis critical. Here we investigate the potential of epigenetic profiles of lung adenocarcinoma, mesothelioma, and non-malignant pulmonary tissues (n=285) as differentiation markers in an analysis of DNA methylation at 1413 autosomal CpG loci associated with 773 cancer-related genes. Using an unsupervised recursively-partitioned mixture modeling technique for all samples, the derived methylation profile classes were significantly associated with sample type (P < 0.0001). In a similar analysis restricted to tumors, methylation profile classes significantly predicted tumor type (P < 0.0001). Random forests classification of CpG methylation of tumors - which splits the data into training and test sets - accurately differentiated MPM from lung adenocarcinoma over 99% of the time (P < 0.0001). In a locus-by-locus comparison of CpG methylation between tumor types, 1266 CpG loci had significantly different methylation between tumors following correction for multiple comparisons (Q < 0.05); 61% had higher methylation in adenocarcinoma. Using the CpG loci with significant differential methylation in a pathways analysis revealed significant enrichment of methylated gene-loci in Cell Cycle Regulation, DNA Damage Response, PTEN Signaling, and Apoptosis Signaling pathways in lung adenocarcinoma when compared to mesothelioma. Methylation-profile-based differentiation of lung adenocarcinoma and mesothelioma is highly accurate, informs on the distinct etiologies of these diseases, and holds promise for clinical application. Mesotheliomas (n=158) and grossly non-tumorigenic parietal pleura (n=18) were obtained following surgical resection at Brigham and Womenâ??s Hospital through the International Mesothelioma Program from a pilot study conducted in 2002 (n=70) and an incident case series beginning in 2005 (n=88) with a participation rate of 85%. We used biopsy specimens from patients treated for NSCLC at the Massachusetts General Hospital from 1992 â?? 1996 (18) including lung adenocarcinomas (n=57) and non-malignant pulmonary tissues (n=48) (of which 22 (39%) were taken from the adenocarcinoma patients) (18). Additional normal lung tissues were obtained from the National Disease Research Interchange from donors free of lung malignancy (n=4).

Dataset Information

DNA methylation profiling of human adrenocortical tumors (ACTs)

Publications

Identification of a CpG island methylator phenotype in adrenocortical carcinomas.

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