Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer

Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options. Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidati...

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Bibliographic Details
Published in:PloS one 2016-03, Vol.11 (3), p.e0150629-e0150629
Main Authors: Legendre, Christophe R, Demeure, Michael J, Whitsett, Timothy G, Gooden, Gerald C, Bussey, Kimberly J, Jung, Sungwon, Waibhav, Tembe, Kim, Seungchan, Salhia, Bodour
Format: Article
Language:English
Subjects:
Aberration
Adrenal Cortex Neoplasms - genetics
Adrenal Cortex Neoplasms - metabolism
Adrenal gland tumors
Adrenal glands
Adrenocortical Carcinoma - genetics
Adrenocortical Carcinoma - metabolism
Analysis
Biology and life sciences
Cancer
Carcinoma
Correlation
Correlation analysis
Deoxyribonucleic acid
Development and progression
DNA
DNA Methylation
DNA, Neoplasm - genetics
DNA, Neoplasm - metabolism
Epigenetics
Female
Gene expression
Gene Expression Regulation, Neoplastic
Gene mutation
Gene regulation
Genes
Genetic aspects
Genomic analysis
Genomics
Humans
Insulin-like growth factors
Male
MARCKS protein
Methylation
Mutation
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Neuroendocrine tumors
p53 Protein
Pathogenesis
Physiological aspects
Signal Transduction
Signaling
Suppressors
Survival
Tissues
Tumor suppressor genes
Tumors
Wnt protein
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Summary:Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options. 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. 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. This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC. DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0150629