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.
Highlights
Adrenocortical carcinomas (ACC) are rare neoplasms that account for up to 0.2% of cancer deaths
DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors
In a study looking at almost 4000 cases of ACC between 1985 and 2005, Bilimoria et al reported 26.5% presented with nodal metastasis and 11.3% presented with distant metastasis, leading to a five-year survival rate of 11.5% compared to 55.1% without distant metastasis [4]
Summary
Adrenocortical carcinomas (ACC) are rare neoplasms that account for up to 0.2% of cancer deaths. The estimated incidence of the disease is 0.7 to 2.0 cases per million persons per year [1, 2]. This disease usually strikes adults in their 40-50s, but may be seen in children, typically with a Tumor Protein p53 (TP53) germline mutation [3]. In a study looking at almost 4000 cases of ACC between 1985 and 2005, Bilimoria et al reported 26.5% presented with nodal metastasis and 11.3% presented with distant metastasis, leading to a five-year survival rate of 11.5% compared to 55.1% without distant metastasis [4]. The response rate to the generally accepted first-line chemotherapy regimen consisting of etoposide, doxibucin, cisplatin and mitotane is only 23% [6], making it clear that there is an urgent need for new therapies
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