Zhuang Z, Ezzat S Z, Vortmeyer A O, Weil R, Oldfield E H, Park W S, Pack S, Huang S, Agarwal S K, Guru S C, Manickam P, Debelenko L V, Kester M B, Olufemi S E, Heppner C, Crabtree J S, Burns A L, Spiegel A M, Marx S J, Chandrasekharappa S C, Collins F S, Emmert-Buck M R, Liotta L A, Asa S L, Lubensky I A
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 1997 Dec 15;57(24):5446-51.
Although pituitary adenomas are monoclonal proliferations, somatic mutations involving genes that govern cell proliferation or hormone production have been difficult to identify. The genetic etiology of most pituitary tumors, therefore, remains unknown. Pituitary adenomas can develop sporadically or as a part of multiple endocrine neoplasia type 1 (MEN1). Recently, the gene responsible for MEN1 was cloned. To elucidate the potential etiological role of the MEN1 gene in pituitary tumorigenesis, 39 sporadic pituitary adenomas from 38 patients and 1 pituitary adenoma from a familial MEN1 patient were examined for MEN1 gene mutations and allelic deletions. Four of 39 sporadic pituitary adenomas showed a deletion of one copy of the MEN1 gene, and a specific MEN1 gene mutation in the remaining gene copy was detected in 2 of these tumors. The corresponding germ-line sequence was normal in all sporadic cases. A specific MEN1 mutation was detected in a pituitary adenoma and corresponding germ-line DNA in a patient with familial MEN1. An allelic deletion of the remaining copy of the MEN1 gene was also found in the patient's tumor. Genetic alterations of the MEN1 gene represent a candidate pathogenetic mechanism of pituitary tumorigenesis. The data suggest that somatic MEN1 gene mutations and deletions play a causative role in the development of a subgroup of sporadic pituitary adenomas.
尽管垂体腺瘤是单克隆增殖性病变，但涉及调控细胞增殖或激素产生的基因的体细胞突变一直难以确定。因此，大多数垂体肿瘤的遗传病因仍不清楚。垂体腺瘤可散发发生，也可作为多发性内分泌腺瘤1型（MEN1）的一部分出现。最近，负责MEN1的基因已被克隆。为了阐明MEN1基因在垂体肿瘤发生中的潜在病因学作用，对38例患者的39个散发性垂体腺瘤和1例家族性MEN1患者的1个垂体腺瘤进行了MEN1基因突变和等位基因缺失检测。39个散发性垂体腺瘤中有4个显示MEN1基因的一个拷贝缺失，其中2个肿瘤在剩余基因拷贝中检测到特定的MEN1基因突变。所有散发病例中相应的种系序列均正常。在1例家族性MEN1患者的垂体腺瘤及相应的种系DNA中检测到特定的MEN1突变。在该患者的肿瘤中还发现了MEN1基因剩余拷贝的等位基因缺失。MEN1基因的遗传改变代表了垂体肿瘤发生的一种潜在致病机制。数据表明，体细胞MEN1基因突变和缺失在散发性垂体腺瘤亚组的发生中起致病作用。
