Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas

Jessica Costa-Guda¹ , Takehiko Tokura¹ , Sanford I Roth² and Andrew Arnold¹

¹Center for Molecular Medicine, University of Connecticut School of Medicine, 263 Farmington Ave, Farmington, Connecticut 06030-3101, USA

²Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02114, USA

author email corresponding author email

BMC Endocrine Disorders 2007, 7:8doi:10.1186/1472-6823-7-8


Published:	4 October 2007

Abstract

Background

The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors.

Methods

We sought acquired mitochondrial DNA mutations by sequencing the entire 16.6 kb mitochondrial genome of each of thirty sporadic parathyroid adenomas (18 chief cell and 12 oxyphil cell), eight independent, polyclonal, parathyroid primary chief cell hyperplasias plus corresponding normal control samples, five normal parathyroid glands, and one normal thyroid gland.

Results

Twenty-seven somatic mutations were identified in 15 of 30 (9 of 12 oxyphil adenomas, 6 of 18 chief cell) parathyroid adenomas studied. No somatic mutations were observed in the hyperplastic parathyroid glands.

Conclusion

Features of the somatic mutations suggest that they may confer a selective advantage and contribute to the molecular pathogenesis of parathyroid adenomas. Importantly, the statistically significant differences in mutation prevalence in oxyphil vs. chief cell adenomas also suggest that mtDNA mutations may contribute to the oxyphil phenotype.