, Volume 38, Issue 7, pp 1730-1737
Date: 08 Feb 2014

Copy Number Variation in CCND1 Gene Is Implicated in the Pathogenesis of Sporadic Parathyroid Carcinoma

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Abstract

Background

The molecular bases for parathyroid carcinomas present in conjunction with sporadic primary hyperparathyroidism are not fully elucidated. Gene copy number variations (CNVs) play an important role in tumorigenesis. The aim of the current study was to explore whether the CNVs of specific tumor-associated genes are involved in parathyroid carcinogenesis.

Methods

A multiplex ligation-dependent probe amplification method was used to compare differences in copy number in 39 common tumor-associated genes among 7 patients with parathyroid carcinoma and 14 age- and sex-matched subjects with parathyroid adenoma.

Results

It was shown that amplification of CCND1, a gene encoding cyclin D1, was more prevalent in parathyroid carcinomas than in adenomas (71 vs. 21 %, p = 0.056). This result was confirmed quantitatively by real-time polymerase chain reaction. Expression of CCND1 mRNA level was significantly higher in carcinomas than in adenomas (p = 0.003). Western blot and immunohistochemical analysis also demonstrated higher expression of CCND1 in carcinoma specimens than in adenoma samples.

Conclusions

It is thus inferred that gain in copy number of CCND1 is implicated in the molecular pathogenesis of parathyroid carcinoma.

Lin Zhao, Li-hao Sun and Dong-mei Liu have contributed equally to this work.