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Aberrant deoxyribonucleic acid methylation in human thyroid tumors
1Department of Medicine, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles 90048.
The Journal of Clinical Endocrinology and Metabolism
|October 1, 1993
Summary
Aberrant DNA methylation is common in benign and malignant thyroid tumors, affecting genes like human GH, PDGFB, and H-ras. These changes may be an early step in thyroid tumor development.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- DNA methylation, a key epigenetic mechanism, involves modifying cytosine residues at CpG sites in vertebrates.
- Aberrant DNA methylation patterns, including hypomethylation and hypermethylation, are hallmarks of human tumors.
- Thyroid neoplasms exhibit diverse methylation profiles, necessitating investigation into specific gene alterations.
Purpose of the Study:
- To investigate aberrant DNA methylation patterns in genes including human GH, platelet-derived growth factor B-chain (PDGFB), and H-ras in benign and malignant human thyroid tumors.
- To determine the prevalence of these methylation changes in different types of thyroid lesions, such as multinodular goiters (MNG), follicular adenomas (FA), and papillary carcinomas (PC).
Main Methods:
- Analysis of DNA methylation status in human thyroid tumor samples (MNG, FA, PC) using gene-specific probes.
- Assessment of methylation in the human GH, PDGFB, and H-ras genes.
- Correlation of methylation abnormalities with tumor type and multiplicity of affected loci.
Main Results:
- Aberrant methylation of the human GH gene was observed in 27% of MNG, 64% of FA, and 63% of PC.
- Abnormal methylation of PDGFB occurred in 31% of MNG, 71% of FA, and 69% of PC.
- The H-ras gene showed complex methylation patterns (primarily hypermethylation) in 27% of MNG, 63% of FA, and 63% of PC. Tumors with methylation abnormalities often displayed changes at multiple gene loci.
Conclusions:
- Benign and malignant thyroid neoplasms exhibit a high frequency of aberrant DNA methylation in selected genes.
- Adenomatous nodules from MNG show a lower prevalence of these aberrant methylation events compared to FA and PC.
- Aberrant DNA methylation is implicated as a potential early event in thyroid tumorigenesis, possibly influencing cell transformation through altered gene expression and genomic stability.