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Genome-scale methylome profiling of adrenocortical carcinomas (ACC) and adenomas (ACA)
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: 
Olivia Barreau Windy Luscap Eric Letouzé Aurélien de Reyniès Nabila Elarouci Jérome Bertherat Guillaume Assié
PROVIDER: E-GEOD-49277 | ArrayExpress | 2014-06-03
SECONDARY ACCESSION(S): GSE49277PRJNA213473
REPOSITORIES: GEO, ArrayExpress
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Project description:Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours has been characterised by mRNA, microRNA and methylation expression signatures but it is unknown if this extends to lncRNAs. We sought to describe lncRNA expression signatures in adrenocortical carcinoma (ACC), adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC). RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using qRT-PCR. Overall design: 21 samples were used in total, 15 cases were included (10 ACCs and 5 ACAs) and compared to 6 controls (NAC). Differentially expressed lncRNAs were selected if they had a minimum fold change of 2.0 up or down regulated and a P-value corrected by the false discovery rate of equal to or less than 0.05.
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Project description:Background: Adrenal myelolipoma (AML) is a relatively common and invariably benign tumor composed of adipose tissue and hematopoietic elements. Due to the variable proportion of fat and hematopoietic elements, it is sometimes challenging to differentiate AML from adrenocortical carcinoma (ACC). MicroRNAs have been identified as promising biomarkers in many tumors, including adrenocortical neoplasms, but the microRNA expression of adrenal myelolipoma has not been investigated, yet. Aims: To perform a large scale microRNA expression profiling in adrenal myelolipoma, benign and malignant adrenocortical tumors to identify potential microRNA biomarkers. Methods: Next-generation sequencing (NGS) on 30 formalin-fixed paraffin-embedded archived tissue samples (discovery cohort: 10 adrenocortical adenoma (ACA), 10 ACC and 10 myelolipoma) was performed by Illumina MiSeq. Significantly differentially expressed microRNAs were validated by real-time RT-qPCR in an independent validation cohort comprised of 10 ACA, 10 myelolipoma and 9 ACC samples. Results: We have found relative overexpression of miR- 451a, miR-486-5p, miR-363-3p and miR-150-5p in myelolipoma compared to the other two tumor groups by NGS. For ACC, we have found up-regulation of miR-184, miR-483-5p, miR-431-5p and miR-183-5p compared to myelolipoma and ACA. Validation by RT-qPCR, confirmed significant overexpression of miR-451a, miR-486-5p and miR-150-5p in myelolipomas relative to ACA and ACC, whereas significant overexpression of miR-184 and miR-183-5p was confirmed in ACC relative to the other 2 groups. The overexpression of miR-483-5p has not turned out to be significant in ACC relative to myelolipomas in the validation cohort. Conclusions: Overexpressed miR-451a, miR-486-5p and miR-150-5p might be potential tissue markers of adrenal myelolipoma. The lack of significance in the expression of miR-483-5p between ACC and myelolipoma is remarkable, as miR-483-5p has been considered to be the best marker of adrenal malignancy to date. Overall design: Altogether 30 samples were investigated by high-throughput microRNA expression profiling
2018-04-07 | GSE112804 | GEO
Project description:Micro-RNA sequencing of adrenocortical tumors and normal adrenal samples. miRNA sequencing of 45 adrenocortical carcinomas (ACC), 30 adrenocortical adenomas (ACA) and 3 normal adrenal samples.
2014-06-01 | E-GEOD-49279 | ArrayExpress
Project description:Micro-RNA sequencing of adrenocortical tumors and normal adrenal samples. Overall design: miRNA sequencing of 45 adrenocortical carcinomas (ACC), 30 adrenocortical adenomas (ACA) and 3 normal adrenal samples.
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Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02 and 0.2 percent of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in approximately 40-70 percent of patients at the time of diagnosis. Standard chemotherapy with mitotane containing regimens is often ineffective and associated with intolerable side-effects. Modern molecular technologies now allow the examination of germ-line and somatic DNA for chromosomal alterations which can give biological insight into cancer processes. Using an array-based high density comparative genomic hybridization (CGH) screen, genomic aberrations within 25 ACC patients were assessed to identify genomic characteristic of this cancer. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. Experiment Overall Design: Array-based high density comparative genomic hybridization (CGH) screen was utilized to identify genomic aberrations within 25 ACC patients. Thirteen tumor samples are from male and 12 are from female patients. The mean age of patients is 51.8 years (range, 23.3-77.7 years) with a median of 54.2 years. The mean tumor physical measurements for the ACC set are a mean weight of 536.3 grams (range, 20.5-2880 grams) and size of 10.7 cm (range, 3-21.5 cm). The clinical data also includes functional status of the tumor which is based on clinical parameters and confirmed by biochemical analysis. Nonfunctional tumors or those that do not over-produce hormones represent 48% of the tumor set. The localization of each tumor is a measure of the tumor metastatic characteristic at time of operation while tumor grade is a histologically based rating system for tumor progression. Sixty percent of the tumors (15 of 25) were localized to the adrenal area with no indication of metastatic spread. The majority of tumors were grade 3 and 4 at time of diagnosis (17 of 25) indicating necrosis and atypical mitosis of >21/50 hpf. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population.
2014-05-02 | E-GEOD-7482 | ArrayExpress
Project description:Genome-scale DNA methylation was analyzed in a cohort of 50 hepatocellular adenomas and 4 normal liver tissues. We performed consensus clustering to identify homogeneous tumor clusters, and we characterized DNA methylation changes in tumor subgroups. Bisulfite converted DNA from 50 fresh frozen hepatocellular adenomas and 4 normal liver samples were hybridized to Illumina HumanMethylation450 BeadChips.
2014-01-13 | E-GEOD-43091 | ArrayExpress
Project description:Context: Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options. Objective: Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC. Design: In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors. Results: This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as tumor suppressor silencing previously unreported in ACC. Conclusions: DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors. Overall design: Bisulphite converted DNA from 24 samples were hybridized to the HumanMethylation450 BeadChip.
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2013-05-22 | E-GEOD-43293 | ArrayExpress
Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02 and 0.2 percent of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in approximately 40-70 percent of patients at the time of diagnosis. Standard chemotherapy with mitotane containing regimens is often ineffective and associated with intolerable side-effects. Modern molecular technologies now allow the examination of germ-line and somatic DNA for chromosomal alterations which can give biological insight into cancer processes. Using an array-based high density comparative genomic hybridization (CGH) screen, genomic aberrations within 25 ACC patients were assessed to identify genomic characteristic of this cancer. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. Keywords: CGH, adrenocortical carcinoma, cancer Overall design: Array-based high density comparative genomic hybridization (CGH) screen was utilized to identify genomic aberrations within 25 ACC patients. Thirteen tumor samples are from male and 12 are from female patients. The mean age of patients is 51.8 years (range, 23.3-77.7 years) with a median of 54.2 years. The mean tumor physical measurements for the ACC set are a mean weight of 536.3 grams (range, 20.5-2880 grams) and size of 10.7 cm (range, 3-21.5 cm). The clinical data also includes functional status of the tumor which is based on clinical parameters and confirmed by biochemical analysis. Nonfunctional tumors or those that do not over-produce hormones represent 48% of the tumor set. The localization of each tumor is a measure of the tumor metastatic characteristic at time of operation while tumor grade is a histologically based rating system for tumor progression. Sixty percent of the tumors (15 of 25) were localized to the adrenal area with no indication of metastatic spread. The majority of tumors were grade 3 and 4 at time of diagnosis (17 of 25) indicating necrosis and atypical mitosis of >21/50 hpf. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population.
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