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Published on: March 14, 2017
Aberrant Histone Methylation Profile in Patients with Sporadic Primary Hyperparathyroidism
Poonam Kumari1, Sanjay Kumar Bhadada1, Ashutosh Kumar Arya2
1Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Histone modifications in parathyroid tumors show a shift towards transcriptional repression, with decreased H3K4me3 and H3K36me3, and increased H3K27me3. These epigenetic changes offer potential therapeutic targets for parathyroid tumors.
Area of Science:
- Epigenetics
- Endocrinology
- Oncology
Background:
- Primary hyperparathyroidism (PHPT) involves elevated parathyroid hormone (PTH) and hypercalcemia.
- Epigenetic modifications, such as histone methylation, influence gene expression in PHPT.
- Global histone modifications in parathyroid tumors are not well understood.
Purpose of the Study:
- To investigate global histone modification profiles in parathyroid tumors.
- To correlate histone modifications with tumor behavior and clinicopathological features.
- To identify molecular pathways linked to histone modifications in parathyroid tumorigenesis.
Main Methods:
- Comparative histone modification profiling using histone H3 multiplex immunoassay in blood and tissue samples from parathyroid adenomas, atypical parathyroid tumors, and parathyroid carcinomas.
- Validation of significantly dysregulated modifications by western blotting.
- Pathway enrichment analysis to identify associated molecular pathways.
Main Results:
- Dynamic alterations in histone H3 modifications were observed across parathyroid tumor phenotypes.
- Reduced H3K4me3 and H3K36me3, and increased H3K27me3 and H3K9me1 were found in tumor samples compared to controls.
- Western blotting confirmed lower H3K4me3 and H3K36me3, and higher H3K27me3 in atypical parathyroid tumors and carcinomas.
- Pathway analysis linked histone modifications to calcium signaling, Wnt, and Hippo signaling pathways.
Conclusions:
- The observed epigenetic changes suggest a shift towards transcriptional repression in parathyroid tumors.
- Increased H3K27me3 and decreased H3K4me3/H3K36me3 indicate potential epigenetic dysregulation in parathyroid tumorigenesis.
- Understanding these mechanisms may lead to novel therapeutic strategies for parathyroid tumors.
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