HRPT2 mutational analysis of typical sporadic parathyroid adenomas.
BACKGROUND
Mutations of HRPT2 are frequent in sporadic parathyroid carcinomas and central to their pathogenesis. However, the potential diagnostic utility of HRPT2 mutation status to distinguish between parathyroid carcinoma and adenoma hinges on the frequency of HRPT2 mutations in benign adenomas. Even a low rate of HRPT2 mutation in adenomas would greatly alter diagnostic specificity, because adenomas are far more prevalent than carcinomas. The issue remains open because of the limited number of typical adenomas, not subjected to additional selection criteria, examined in previous studies.


OBJECTIVE
To determine the frequency of HRPT2 somatic mutations in a substantial series of typical, sporadic parathyroid adenomas, we directly sequenced coding and flanking splice junctional regions of all HRPT2 exons in solitary adenomas from 60 patients.


CONCLUSIONS
No intragenic HRPT2 mutations were detected, strengthening the degree of specificity of HRPT2 mutation as a feature of sporadic parathyroid carcinoma as opposed to sporadic adenomas. Our observations encourage additional study of the diagnostic potential of HRPT2 in parathyroid neoplasia and support the view that HRPT2 inactivation is not an important participant in the pathogenesis of typical parathyroid adenomas.
Krebs
Linda J
LJ
Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030-3101, USA.
Shattuck
Trisha M
TM
Arnold
Andrew
A
D000236:Adenoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009154:Mutation; D010282:Parathyroid Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C454900:CDC73 protein, human; D004274:DNA, Recombinant; D025521:Tumor Suppressor Proteins