Differential methylation signature in benign and malignant cortisol producing adrenocortical tumors
T. Åkerström, T. Ahmad, P. Hellman & P. Björklund
Background: Adrenocortical carcinomas (ACC) are rare tumors with an incidence of 12 per million. Although rare, it is an aggressive endocrine cancer with poor prognosis. As of today there is no reliable diagnostic biomarker to distinguish benign tumors from malignant tumors. Global changes in DNA methylation and DNA promoter hypermethylation are important events in tumorigenesis. Promoter hypermethylation can cause silencing of tumour suppressor genes or lead to abnormal function of important cellular pathways. The purpose of this study was to investigate the changes in DNA methylation in cortisol producing adrenocortical carcinoma compared to benign cortisol producing adenomas.
Methods: DNA was extracted from 16 adrenocortical tumors and methylataion status was analyzed using the Infinium Human Methylation 450K BeadChip. Total RNA was isolated from 30 tumors, converted to cDNA and mRNA expression was analyzed by q-PCR using SYBR Green and GAPDH as internal control.
Results and discussion: Unsupervised hierarchical clustering showed an altered DNA methylation profile in ACCs compared to adenomas. CYP1B1, OTX1 and RASAL1 were identified as some of the most differentially hypermethylated genes. Aberrant methylation of CYP1B1 has been previously reported in nodular goiter, colorectal cancer and gastric carcinomas. CYP1B1 mRNA expression was significantly reduced in ACCs compared to adenomas. However, no significant difference in mRNA expression was observed for OTX1 and RASAL1. In conclusion, mRNA expression of CYP1B1 was significantly reduced in cortisol producing adrenocortical carcinomas compared to adenomas, expression of CYP1B1 might be used as a biomarker in distinguishing aggressive tumors from benign ones and also provide outlines for choosing the appropriate treatment.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.