Mutations of the MEN1 tumor suppressor gene in pituitary tumors.
Mutations of the MEN1 tumor suppressor gene in pituitary tumors.
复制标题
垂体瘤中 MEN1 抑癌基因的突变。
作者：
Z. Zhuang;S. Ezzat;A. Vortmeyer;R. Weil;E. Oldfield;W. Park;S. Pack;Steve C Huang;S. Agarwal;S. Guru;P. Manickam;L. Debelenko;M. Kester;S. Olufemi;C. Heppner;J. Crabtree;A. Burns;A. Spiegel;S. Marx;S. Chandrasekharappa;F. Collins;M. Emmert;L. Liotta;S. Asa;I. Lubensky
虽然垂体腺瘤是单克隆增生，但涉及控制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，大多数垂体瘤的遗传病因仍不清楚。垂体腺瘤可以偶发或作为多发性1型内分泌瘤（MEN1）的一部分。最近，MEN1基因被克隆。为了阐明MEN1基因在垂体肿瘤发生中的潜在病因学作用，我们对38例患者的39例散发性垂体腺瘤和1例家族性MEN1患者的垂体腺瘤进行了MEN1基因突变和等位基因缺失的检测。39例散发性垂体腺瘤中有4例显示MEN1基因拷贝缺失，其中2例在其余基因拷贝中检测到特异性MEN1基因突变。在所有散发病例中，相应的种系序列正常。在家族性MEN1患者的垂体腺瘤和相应的种系DNA中检测到特异性MEN1突变。在患者的肿瘤中也发现了MEN1基因剩余拷贝的等位基因缺失。MEN1基因的遗传改变是垂体肿瘤发生的一种候选发病机制。这些数据表明，体细胞MEN1基因突变和缺失在散发性垂体腺瘤亚群的发展中起着致病作用。
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.
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影响因子：
5.8
作者：
HERMAN, V;FAGIN, J;MELMED, S
通讯作者：
MELMED, S
影响因子：
4.4
作者：
SHEFFIELD, VC;BECK, JS;STONE, EM
通讯作者：
STONE, EM
DOI：
10.1073/pnas.91.21.9700
发表时间：
1994-10-11
影响因子：
11.1
作者：
HERMAN, JG;LATIF, F;BAYLIN, SB
通讯作者：
BAYLIN, SB
影响因子：
15.9
作者：
ALEXANDER, JM;BILLER, BMK;KLIBANSKI, A
通讯作者：
KLIBANSKI, A
人类泌乳素瘤和垂体癌中的 ras 突变。
DOI：
10.1210/jcem.78.1.8288721
发表时间：
1994
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Cai,WY;Alexander,JM;Hedley-Whyte,ET;Scheithauer,BW;Jameson,JL;Zervas,NT;Klibanski,A
通讯作者：
Klibanski,A