年轻发病的散发性垂体大腺瘤的种系遗传变异:多基因面板分析

IF 4.2 Q1 ENDOCRINOLOGY & METABOLISM
Leonor M. Gaspar , Catarina I. Gonçalves , Ema L. Nobre , Fernando Fonseca , Cláudia Amaral , João S. Duarte , Luísa Raimundo , Catarina Saraiva , Luísa Cortez , Olinda Marques , Manuel C. Lemos
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引用次数: 0

摘要

一些基因的突变与家族性垂体腺瘤有关。散发的垂体腺瘤(即没有家族史或共存的内分泌肿瘤)也偶尔被发现是由这些基因的种系突变引起的,特别是在肿瘤较大的年轻患者中。本研究的目的是确定年轻发病的散发性垂体大腺瘤患者种系突变的频率。通过全外显子组测序(WES)对年龄在40岁之前诊断为散发性垂体大腺瘤的225名葡萄牙患者进行队列研究,随后对与垂体腺瘤易感性相关的29个基因进行虚拟面板分析。在16例(7.1%)患者中发现致病性和可能致病性变异。影响基因为AIP (n = 4)、PMS2 (n = 4)、MEN1 (n = 2)、VHL (n = 2)、CDH23 (n = 1)、MSH2 (n = 1)、SDHB (n = 1)、TP53 (n = 1)。在30岁以下和18岁以下的患者中,致病性变异和可能致病性变异的频率分别增加到9.0%和12.0%。这是迄今为止对年轻发病的散发性垂体大腺瘤患者进行的最大的多基因分析。我们证实AIP是最常见的基因,但也发现了罕见的垂体腺瘤的遗传原因。结果可能有助于更好地了解这些肿瘤的遗传景观,并有助于决定哪些基因包括在年轻发病的垂体大腺瘤患者的遗传筛查中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis
Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic pituitary adenomas (i.e. with no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations in these genes, especially in young patients with larger tumours. The aim of this study was to determine the frequency of germline mutations in patients with young-onset sporadic pituitary macroadenomas. A cohort of 225 Portuguese patients with sporadic pituitary macroadenomas diagnosed before the age of 40 years was studied by whole exome sequencing (WES) followed by the analysis of a virtual panel of 29 genes that have been associated with predisposition to pituitary adenomas. Pathogenic and likely pathogenic variants were identified in 16 (7.1 %) of patients. The affected genes were AIP (n = 4), PMS2 (n = 4), MEN1 (n = 2), VHL (n = 2), CDH23 (n = 1), MSH2 (n = 1), SDHB (n = 1), and TP53 (n = 1). In patients diagnosed under the ages of 30 and 18 years, the frequency of pathogenic and likely pathogenic variants increased to 9.0 % and 12.0 %, respectively. This is so far the largest multigene analysis of patients with young-onset sporadic pituitary macroadenomas. We confirmed the AIP as the most frequently involved gene, but also uncovered rarer genetic causes of pituitary adenomas. The results may contribute to a better understanding of the genetic landscape of these tumours and help to decide which genes to include in the genetic screening of patients with young-onset pituitary macroadenomas.
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来源期刊
CiteScore
6.10
自引率
0.00%
发文量
24
审稿时长
16 weeks
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