Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Center of Thyroid and Parathyroid, Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Endocrinology. 2018 Aug 1;159(8):3061-3068. doi: 10.1210/en.2018-00246.
Primary hyperparathyroidism is commonly caused by excess production of parathyroid hormone from sporadic parathyroid adenomas. However, the genetic architecture of sporadic primary hyperparathyroidism remains largely uncharacterized, especially in the Chinese population. To identify genetic abnormalities that may be involved in the etiology of sporadic parathyroid adenomas and to determine the mutation frequency of previously identified genes in the Chinese population, we performed whole-exome sequencing of 22 blood-tumor pairs from sporadic parathyroid adenomas. The most important finding is the recurrently mutated gene, ASXL3, which has never been reported in parathyroid tumors before. Moreover, we identified two different somatic mutations in the CDC73 gene and one somatic mutation in the EZH2 gene. The Y54X mutation in the CDC73 gene was previously identified in parathyroid carcinomas, which proved that parathyroid adenomas and carcinomas might possess similar molecular signatures. No mutations in the MEN1 or CCND1 genes were observed in our study. Thus, our data provide insights into the genetic pathogenesis of sporadic parathyroid adenomas and are valuable for the development of diagnostic and therapeutic approaches for sporadic primary hyperparathyroidism.
原发性甲状旁腺功能亢进症通常是由甲状旁腺腺瘤中甲状旁腺激素的过度产生引起的。然而，散发性原发性甲状旁腺功能亢进症的遗传结构在很大程度上仍未被描述，特别是在中国人群中。为了确定可能参与散发性甲状旁腺腺瘤发病机制的遗传异常，并确定先前在中国人群中已鉴定基因的突变频率，我们对 22 对来自散发性甲状旁腺腺瘤的血液-肿瘤对进行了全外显子组测序。最重要的发现是反复突变的基因 ASXL3，以前从未在甲状旁腺瘤中报道过。此外，我们在 CDC73 基因中鉴定出两个不同的体细胞突变，在 EZH2 基因中鉴定出一个体细胞突变。CDC73 基因中的 Y54X 突变以前在甲状旁腺癌中被发现，这证明甲状旁腺腺瘤和癌可能具有相似的分子特征。在我们的研究中没有观察到 MEN1 或 CCND1 基因的突变。因此，我们的数据提供了对散发性甲状旁腺腺瘤遗传发病机制的深入了解，对开发散发性原发性甲状旁腺功能亢进症的诊断和治疗方法具有重要价值。
