Increased global Alu hypomethylation affect distant metastatic, dedifferentiated thyroid cancer
Global hypomethylation of Alu appears to increasingly influence distant metastatic differentiated thyroid cancer (DTC), poorly (P)DTC and anaplastic (A)TC, according to a recent study. This suggests that the epigenetic entity may be involved in thyroid cancer progression and dedifferentiation.
A total of 90 primary thyroid tumours (28 low-risk DTC, 13 paediatric DTC, 33 distant metastatic DTC, seven PDTC and nine ATC), as well as 24 distant metastases and 20 normal thyroid tissues, were included in this analysis.
There was an increasing hypomethylation for distant metastatic DTC (median, 4.0; interquartile range [IQR], 3.1‒6.2) and PDTC/ATC (median, 9.3; IQR, 7.0‒12.1) as compared with normal thyroid tissue (median, 2.75; IQR, 2.30‒3.15). However, hypomethylation did not affect low-risk and paediatric DTC.
Alu hypomethylation was comparable between distant metastases and matched primary tumours. Furthermore, Alu hypomethylation was increased in BRAF compared with RAS mutated tumours.
Kaplan-Meier and Cox regression analyses showed an association between tumour hypomethylation and thyroid cancer-related and all-cause mortality, but such association was lost after adjustment for thyroid cancer risk category.
This study sought to examine the role of global hypomethylation of Alu in thyroid cancer progression and its potential as a prognostic marker. The Quantification of Unmethylated Alu technique was applied to assess global Alu repeats, which were used as a surrogate marker for DNA global hypomethylation. Sanger sequencing determined the mutations in BRAF and RAS.
“Global DNA hypomethylation is a major event for the development and progression of cancer, although the significance in thyroid cancer remains unclear,” researchers said.