Global DNA methylation profile in medullary thyroid cancer patients

Background: Changes in global DNA methylation have been suggested to cause genomic instability leading to increased risk of cancer. The accumulation of epigenetic changes is believed to contribute to tumorigenesis and dedifferentiation, but the effects of such changes in thyroid cancer are still yet defined. Objective: To evaluate the global DNA methylation levels in thyroid cancer patients. Methods: Total DNA was extracted from peripheral blood leukocytes of the medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) patients and the methylation pattern was evaluated using the Imprint Methylated DNA Quantification kit (Sigma-Aldrich). Results: A total of 42 patients were analyzed (24 MTC, 12 PTC, and 6 controls). For MTC, the mean age was 41 +/- 20 years, 54% were women and 12 cases were sporadic. The median calcitonin level at diagnosis was 1692 (637-8865), 65% of the MTC patients had local metastases and 23% distant metastases. For PTC, the median age was 43 +/- 15 years, 58% were women and 50% had local metastases. The percentage of overall methylation differed according to the tumor subtype. Patients with MTC had a higher level of DNA methylation when compared to individuals with PTC (35 (24-48) vs. 17 (6.5-20.5); P = 0.002, respectively). Interestingly, among patients with MTC, individuals with the sporadic form of the disease had a higher level of methylation when compared to the hereditary form (25 (16-37) vs. 43 (33-52); P = 0.025, respectively). No association was observed between global methylation levels and clinical and/or oncological characteristics of the disease. Conclusion: Global methylation levels were higher in MTC as compared to PTC patients. These results suggest the overall DNA methylation profile may be influenced by the histological subtype of thyroid cancer.