Expression of CASR, GCM2 and PAX1 and their promoter methylation status in sporadic parathyroid adenoma.
Singh P, Arya AK, Dahiya D, Sachdeva N, Saikia UN, Sood A, Bhansali A, Rao SD, and Bhadada S. Expression of CASR, GCM2 and PAX1 and their promoter methylation status in sporadic parathyroid adenoma. Endocr Rev 2018; 39(2)
Introduction: Loss of CASR has been well reported in parathyroid adenoma but the transcription factors i.e. GCM2 and PAX1 associated to CASR expression are not studied. Thus, aim of the study is to evaluate expression of CASR, GCM2 and PAX1 with their promoter DNA methylation analysis as a possible cause in sporadic parathyroid adenoma. Materials and methods: A total of 20 parathyroid adenoma and 5 normal parathyroid tissue were recruited for the study. Gene expression analysis was done by quantitative real time PCR and DNA promoter methylation was performed by bisulphite sequencing PCR. Results: The quantitative real time PCR analysis showed significantly reduced expression of CASR, GCM2 and PAX1 in parathyroid adenoma when compared to normal parathyroid samples with fold reduction of 0.31±0.22 (p ≤0.0001), 0.28±0.23 (p ≤0.0001) and 0.31±0.27 (p ≤0.0001) respectively. However, gene expression of CASR was positively correlated to tumor weight (ρ = 0.616; p = 0.047) but not with other clinicopathological parameters. Promoter regions of CASR, GCM2 and PAX1 as determined by bisulphite sequencing displayed significant hypermethylation in 70% (14/20), 60% (12/20) and 60% (12/20) in sporadic parathyroid adenoma cases respectively. No methylation was observed in control subjects. Correlation analysis revealed that promoter methylation of GCM2 was inversely related to its gene expression (ρ = -0.68; p = 0.018) but not with other clinicopathological parameters of the patients. Conclusion: Our study reported the altered expression of CASR as well as its transcription factors i.e. GCM2 and PAX1 in parathyroid adenoma. Promoter hypermethylation of CASR, GCM2 and PAX1 might play role in altered expression of these genes during tumorigenesis of sporadic parathyroid adenoma.