Arnold A, Motokura T, Bloom T, Rosenberg C, Bale A, Kronenberg H, Ruderman J, Brown M, Kim H G
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114.
Henry Ford Hosp Med J. 1992;40(3-4):177-80.
Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the most tightly linked MEN 1 markers, by pulsed field gel electrophoresis. PRAD1 may, in fact, be the long-sought BCL-1 lymphoma oncogene. PRAD1 encodes a novel type of cyclin protein and thus may normally function in controlling the cell cycle, perhaps through direct interaction with cdc2 or a related kinase. PRAD1's possible primary, or more likely secondary, involvement in the pathogenesis of MEN 1-related tumors is unknown and under investigation.
甲状旁腺功能亢进是1型多发性内分泌腺瘤病（MEN 1）的核心组成部分，散发性和家族性甲状旁腺疾病可能具有某些共同的致病特征。我们最近在一部分散发性甲状旁腺腺瘤中发现了一个与甲状旁腺激素（PTH）基因座发生克隆重排的基因。这个候选癌基因PRAD1（以前称为D11S287），似乎以一种类似于B淋巴细胞肿瘤中免疫球蛋白基因的组织特异性增强子重排激活C-MYC或BCL-2的方式，促进甲状旁腺肿瘤的发生。PRAD1基因定位于11q13，通过脉冲场凝胶电泳已与BCL-1断裂位点相关联，尽管与最紧密连锁的MEN 1标记物无关。实际上，PRAD1可能就是长期以来寻找的BCL-1淋巴瘤癌基因。PRAD1编码一种新型的细胞周期蛋白，因此可能通常在控制细胞周期中发挥作用，也许是通过与cdc2或相关激酶直接相互作用来实现。PRAD1在MEN 1相关肿瘤发病机制中可能的原发性，或者更可能是继发性作用尚不清楚，正在研究中。
