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Analysis of Microsatellite Instability in Sporadic Parathyroid Adenomas

Center for Molecular Medicine and Division of Endocrinology and Metabolism, University of Connecticut School of Medicine (S.M.M., J.J.G., A.A.), and Department of Oral Diagnosis, University of Connecticut School of Dental Medicine (S.M.M.), Farmington, Connecticut 06030

Address all correspondence and requests for reprints to: Andrew Arnold, M.D., Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT 06030-3101. E-mail: aarnold{at}nso2.uchc.edu.

Microsatellite instability (MSI) is the form of genomic instability associated with defective DNA mismatch repair (MMR) in human tumorigenesis. Recent reports have suggested a role for MSI in the pathogenesis of sporadic parathyroid adenomas. However, because of their small sample sizes and/or lack of systematic analysis of genome-wide MSI, these studies have not provided conclusive evidence that MMR defects are a common occurrence in parathyroid neoplasia. To further investigate whether MSI plays an important role in parathyroid tumorigenesis, we analyzed 49 sporadic parathyroid adenomas for MSI using a panel of 5 microsatellite DNA markers that has been recommended for sensitive detection of MSI by the NCI Workshop and validated in other tumor types. These microsatellite loci were amplified by PCR using fluorescent-labeled primers from the 49 samples of template tumor DNA and matching normal DNA isolated from the same patients’ peripheral blood leukocytes. None of the 49 tumors showed evidence of MSI at any of the analyzed loci of the NCI marker panel. These observations strongly suggest that defective DNA MMR plays a minor role, if any, in the pathogenesis of sporadic parathyroid adenomas.

This work was supported in part by Grant DE14773 from the National Institute of Dental and Craniofacial Research (to S.M.), the John G. Haddad, Jr. Award from The Paget Foundation (to A.A. and S.M.), and the Murray-Heilig Fund in Molecular Medicine (to A.A.).

Abbreviations: MMR, Mismatch repair; MSI, microsatellite instability; MSI-H, high frequency microsatellite instability; MSI-L, low frequency microsatellite instability; MSS, microsatellite stable.