Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer |
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| Authors: | Christophe R. Legendre Michael J. Demeure Timothy G. Whitsett Gerald C. Gooden Kimberly J. Bussey Sungwon Jung Tembe Waibhav Seungchan Kim Bodour Salhia |
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| Affiliation: | 1. Translational Genomics Research Institute, Phoenix, AZ, United States of America;2. NantOmics, LLC, Phoenix, Arizona, United States of America;3. Department of Genome Medicine and Science, Gachon University School of Medicine, Incheon, 21565, Republic of Korea;4. Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, 21565, Republic of Korea;CEA - Institut de Genomique, FRANCE |
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| Abstract: | ContextAdrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options.ObjectiveUnderstanding 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.DesignIn 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.ResultsThis 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.ConclusionsDNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors. |
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