Large genomic deletions in AIP in pituitary adenoma predisposition
Large genomic deletions in AIP in pituitary adenoma predisposition
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DOI：
10.1210/jc.2008-1003
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发表时间：
2008-10-01
影响因子：
5.8
通讯作者：
Aaltonen, Lauri A.
中科院分区：
文献类型：
--
作者：
Georgitsi, Marianthi;Heliovaara, Elina;Aaltonen, Lauri A.
背景：AIP的胚系突变最近被证明是导致垂体腺瘤易感性(PAP)的原因。目的：我们的目标是评估大的基因组种系AIP缺失在PAP中的可能作用。AIP是肿瘤易感综合征中的一种重要突变类型。设计：在这里，我们应用多重连接依赖的探针扩增方法来检查大的基因组AIP或MEN1突变是否占PAP病例的一个子集。患者：这项研究是针对起源于欧洲的家族性和散发性的垂体腺瘤病例，通过测序发现其种系AIP和MEN1突变为阴性。结果：21个垂体腺瘤家族中有两个(9.5%)存在AIP缺失。在67例散发性垂体腺瘤患者中未检测到拷贝数变化。未发现MEN1缺失。结论：本研究显示大的基因组AIP缺失是PAP的一个子集。因此，在接受咨询和AIP基因检测的疑似PAP病例中，如果直接测序没有发现突变，可以考虑多重连接依赖的探针扩增。
Context: Germline mutations in AIP have been recently shown to cause pituitary adenoma predisposition (PAP). Subsequently, many intragenic germline mutations have been reported, both in familial and in sporadic settings.Objective: Our objective was to evaluate the possible contribution of large genomic germline AIP deletions, an important mutation type in tumor predisposition syndromes, in PAP.Design: Here, we applied the multiplex ligation-dependent probe amplification assay to examine whether large genomic AIP or MEN1 alterations account for a subset of PAP cases.Patients: The study was performed on familial and sporadic pituitary adenoma cases of European origin, which had previously tested negative for germline AIP and MEN1 mutations by sequencing.Results: Two of 21 pituitary adenoma families (9.5%) were found to harbor an AIP deletion. No copy number changes were detected among 67 sporadic pituitary adenoma patients. No MEN1 deletions were found.Conclusions: The present study shows that large genomic AIP deletions account for a subset of PAP. Therefore, in suspected PAP cases undergoing counseling and AIP genetic testing, multiplex ligation-dependent probe amplification could be considered if direct sequencing does not identify a mutation.