Barlier Anne, Vanbellinghen Jean-François, Daly Adrian F, Silvy Monique, Jaffrain-Rea Marie-Lise, Trouillas Jacqueline, Tamagno Gianluca, Cazabat Laure, Bours Vincent, Brue Thierry, Enjalbert Alain, Beckers Albert
Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart Tilman, 4000 Liège, Belgium.
J Clin Endocrinol Metab. 2007 May;92(5):1952-5. doi: 10.1210/jc.2006-2702. Epub 2007 Feb 13.
Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel mutations of this gene have since been identified in familial isolated pituitary adenoma cohorts.
The objective of the study was to undertake full AIP coding sequence screening to assess for the presence of germline and somatic mutations in European Union subjects with sporadic pituitary tumors.
The study design was the analysis of DNA from peripheral blood lymphocytes and analysis of exons 1-6 and paraexonic intron sequences of AIP. Multiplex ligation-dependent probe amplification was used to screen separate sporadic pituitary tumor tissue samples for discrete and extensive deletions or mutations of the AIP gene.
The study was conducted in university tertiary referral Clinical Genetics, Molecular Biology, and Endocrinology Departments.
In 107 patients [prolactinomas (n =49), nonfunctioning tumors (n = 29), somatotropinomas (n = 26), ACTH-secreting tumors (n = 2), TSH-secreting tumors (n = 1)], no germline mutations of AIP were demonstrated. Among a group of 41 tumor samples from other subjects, a novel AIP mutation (R22X) was found in one sample in which the corresponding allele was deleted; follow-up screening of the patient demonstrated a germline R22X AIP mutation.
AIP mutations do not appear to play a prominent role in sporadic pituitary tumorigenesis in this population of European subjects.
有限的筛查表明，芳烃受体相互作用蛋白（AIP）基因中的三种种系突变与散发性垂体瘤的发生无关。此后，在家族性孤立性垂体腺瘤队列中已鉴定出该基因的多个新突变。
本研究的目的是对AIP编码序列进行全面筛查，以评估散发性垂体瘤的欧盟受试者中种系和体细胞突变的存在情况。
本研究设计为对外周血淋巴细胞的DNA进行分析，并对AIP的外显子1-6和外显子旁内含子序列进行分析。采用多重连接依赖探针扩增技术，对散发性垂体瘤组织样本进行筛查，以检测AIP基因的离散和广泛缺失或突变。
本研究在大学三级转诊临床遗传学、分子生物学和内分泌科进行。
在107例患者中[催乳素瘤（n = 49）、无功能肿瘤（n = 29）、生长激素瘤（n = 26）、促肾上腺皮质激素分泌肿瘤（n = 2）、促甲状腺激素分泌肿瘤（n = 1）]，未发现AIP的种系突变。在一组来自其他受试者的41个肿瘤样本中，在一个样本中发现了一种新的AIP突变（R22X），其中相应的等位基因被删除；对该患者的后续筛查显示存在种系R22X AIP突变。
在这群欧洲受试者中，AIP突变似乎在散发性垂体瘤的发生中不发挥突出作用。
