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散发性垂体瘤中men1肿瘤抑制基因的分子特征

Molecular characterization of the men1 tumor suppressor gene in sporadic pituitary tumors.

作者信息

Prezant T R, Levine J, Melmed S

机构信息

Division of Endocrinology and Metabolism, Cedars-Sinai Research Institute, University of California, Los Angeles, USA.

出版信息

J Clin Endocrinol Metab. 1998 Apr;83(4):1388-91. doi: 10.1210/jcem.83.4.4859.

Abstract

Anterior pituitary tumors arise sporadically, and also as part of the inherited multiple endocrine neoplasia type 1 (MEN 1) syndrome. To investigate the role of the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete coding sequence was screened for mutations in 45 sporadic anterior pituitary tumors, including 14 hormone-secreting tumors and 31 nonsecreting tumors, by dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were found in the men1 coding region. The men1 gene was expressed in 43 of these tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH) for several polymorphic markers on chromosomal region 11q13. Furthermore, both alleles were expressed in 19 tumors in which the constitutional DNA was heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor suppressor gene, by mutation or by imprinting, does not appear to play a prominent role in sporadic pituitary adenoma pathogenesis.

摘要

垂体前叶肿瘤可散发性发生,也可作为遗传性多发性内分泌腺瘤1型(MEN 1)综合征的一部分出现。为了研究最近分离出的men1基因在散发性垂体肿瘤发生中的作用,通过双脱氧指纹图谱和序列分析,对45例散发性垂体前叶肿瘤(包括14例分泌激素肿瘤和31例无分泌功能肿瘤)的完整编码序列进行了突变筛查。在men1编码区未发现致病序列改变。在其中43例有足够RNA的肿瘤中检测到men1基因表达,其中1例肿瘤在染色体区域11q13上的几个多态性标记出现杂合性缺失(LOH)。此外,在19例肿瘤中,两个等位基因均有表达,其组成性DNA在基因内多态性方面为杂合子。因此,men1肿瘤抑制基因通过突变或印记失活似乎在散发性垂体腺瘤发病机制中不发挥突出作用。

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