Risk category system to identify pituitary adenoma patients with AIP mutations.
Risk category system to identify pituitary adenoma patients with AIP mutations.
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DOI：
10.1136/jmedgenet-2017-104957
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发表时间：
2018-04
影响因子：
4
通讯作者：
International FIPA consortium
中科院分区：
文献类型：
--
作者：
Caimari F;Hernández-Ramírez LC;Dang MN;Gabrovska P;Iacovazzo D;Stals K;Ellard S;Korbonits M;International FIPA consortium
用于识别患有垂体腺瘤相关基因突变风险的患者的预测工具在临床实践中非常有帮助。因此，我们的目标是开发和验证垂体腺瘤患者芳烃受体相互作用蛋白（AIP）突变的可靠风险分类系统。在2007年至2016年期间连续招募了2227名受试者的国际队列，包括垂体腺瘤患者（家族性和散发性）及其亲属。对所有先证者（n=1429）进行AIP突变筛查，前瞻性诊断为垂体腺瘤的患者（n=24）作为其临床筛查的一部分，从分析中排除。进行单变量分析，比较有和无AIP突变的患者。基于多元逻辑回归模型，六个潜在的因素被确定为一个风险分类系统的发展，个人风险分为低风险，中度风险和高风险类别。内部交叉验证测试用于验证系统。1405例患者有垂体瘤，其中43%有阳性家族史，55.5%有生长激素瘤，81.5%有大腺瘤。总体而言，134例患者有AIP突变（9.5%）。我们确定了AIP突变存在的四个独立预测因素：发病年龄，0-18岁的比值比（OR）为14.34，家族史（OR 10.85），生长激素过量（OR 9.74）和大肿瘤大小（OR 4.49）。在我们的队列中，71%的患者被确定为低风险（AIP突变风险<5%），9.2%为中度风险，20%为高风险（风险≥20%）。实现了良好的区分度（c-统计量=0.87）和内部验证。我们提出了一个用户友好的风险分类系统，可以可靠地将患者分为高风险，中等风险和低风险组的AIP突变的存在，从而提供指导，以确定患者携带AIP突变的高风险。该风险评分基于AIP突变高患病率的队列，应谨慎应用于其他人群。
Predictive tools to identify patients at risk for gene mutations related to pituitary adenomas are very helpful in clinical practice. We therefore aimed to develop and validate a reliable risk category system for aryl hydrocarbon receptor-interacting protein (AIP) mutations in patients with pituitary adenomas. An international cohort of 2227 subjects were consecutively recruited between 2007 and 2016, including patients with pituitary adenomas (familial and sporadic) and their relatives. All probands (n=1429) were screened for AIP mutations, and those diagnosed with a pituitary adenoma prospectively, as part of their clinical screening (n=24), were excluded from the analysis. Univariate analysis was performed comparing patients with and without AIP mutations. Based on a multivariate logistic regression model, six potential factors were identified for the development of a risk category system, classifying the individual risk into low-risk, moderate-risk and high-risk categories. An internal cross-validation test was used to validate the system. 1405 patients had a pituitary tumour, of which 43% had a positive family history, 55.5% had somatotrophinomas and 81.5% presented with macroadenoma. Overall, 134 patients had an AIP mutation (9.5%). We identified four independent predictors for the presence of an AIP mutation: age of onset providing an odds ratio (OR) of 14.34 for age 0-18 years, family history (OR 10.85), growth hormone excess (OR 9.74) and large tumour size (OR 4.49). In our cohort, 71% of patients were identified as low risk (<5% risk of AIP mutation), 9.2% as moderate risk and 20% as high risk (≥20% risk). Excellent discrimination (c-statistic=0.87) and internal validation were achieved. We propose a user-friendly risk categorisation system that can reliably group patients into high-risk, moderate-risk and low-risk groups for the presence of AIP mutations, thus providing guidance in identifying patients at high risk of carrying an AIP mutation. This risk score is based on a cohort with high prevalence of AIP mutations and should be applied cautiously in other populations.
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影响因子：
5.8
作者：
Daly, Adrian F.;Tichomirowa, Maria A.;Beckers, Albert
通讯作者：
Beckers, Albert
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
7.1
作者：
Iacovazzo D;Caswell R;Bunce B;Jose S;Yuan B;Hernández-Ramírez LC;Kapur S;Caimari F;Evanson J;Ferraù F;Dang MN;Gabrovska P;Larkin SJ;Ansorge O;Rodd C;Vance ML;Ramírez-Renteria C;Mercado M;Goldstone AP;Buchfelder M;Burren CP;Gurlek A;Dutta P;Choong CS;Cheetham T;Trivellin G;Stratakis CA;Lopes MB;Grossman AB;Trouillas J;Lupski JR;Ellard S;Sampson JR;Roncaroli F;Korbonits M
通讯作者：
Korbonits M
影响因子：
3.9
作者：
Daly, Adrian F.;Yuan, Bo;Beckers, Albert
通讯作者：
Beckers, Albert
影响因子：
5.8
作者：
Daly, Adrian F.;Rixhon, Martine;Beckers, Albert
通讯作者：
Beckers, Albert