Mutational Analysis of ZFY in Sporadic Parathyroid Adenomas

CONTEXT: The molecular pathogenesis of sporadic parathyroid adenomas is incompletely understood, with alterations in cyclin D1/PRAD1 and MEN1 most firmly established as genetic drivers. The gene encoding the X-linked zinc finger protein (ZFX) has recently been implicated in the pathogenesis of a subset of parathyroid adenomas after recurrent, hotspot-focused somatic mutations were identified. ZFX escapes X inactivation and is transcribed from both alleles in women, and a highly homologous gene encoding the Y-linked zinc finger protein (ZFY) provides dosage compensation in males. OBJECTIVE: We sought to investigate the role of ZFY mutation in sporadic parathyroid adenoma. INTERVENTION: Polymerase chain reaction and Sanger sequencing were used to examine DNA from typically presenting, sporadic (nonfamilial, nonsyndromic) parathyroid adenomas from male patients for mutations within the ZFY gene. RESULTS: No mutations were identified among 117 adenomas. CONCLUSIONS: The absence of ZFY mutations in this series suggests that ZFY rarely, if ever, acts as a driver oncogene in sporadic parathyroid adenomas. The apparent differences in tumorigenic capabilities between the closely related zinc finger proteins ZFX and ZFY suggest that structure-function studies could represent an opportunity to gain insight into neoplastic processes in the parathyroid glands.