Araujo Paula Bruna, Kasuki Leandro, de Azeredo Lima Carlos Henrique, Ogino Liana, Camacho Aline H S, Chimelli Leila, Korbonits Márta, Gadelha Monica R
Department of Internal Medicine and Endocrine UnitMedical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
Diagnósticos da América SARio de Janeiro, Rio de Janeiro, Brazil.
Endocr Connect. 2017 Nov;6(8):914-925. doi: 10.1530/EC-17-0237. Epub 2017 Oct 26.
Aryl hydrocarbon receptor-interacting protein () gene mutations () are the most frequent germline mutations found in apparently sporadic pituitary adenomas (SPA). Our aim was to evaluate the frequency of among young Brazilian patients with SPA. We performed an observational cohort study between 2013 and 2016 in a single referral center. screening was carried out in 132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of any size diagnosed until 18 years of age. Twelve tumor samples were also analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire -coding region for evaluation of mutations. Eleven (8.3%) of the 132 patients had , comprising 9/74 (12%) somatotropinomas, 1/38 (2.6%) prolactinoma, 1/10 (10%) corticotropinoma and no non-functioning adenomas. In pediatric patients (≤18 years), frequency was 13.3% (2/15). Out of the 5 patients with gigantism, two had , both truncating mutations. The Y268* mutation was described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation in our patient. No somatic mutations were found in the 12 tumor samples. A tumor sample from an acromegaly patient harboring the A299V showed loss of heterozygosity. In conclusion, frequency in SPA Brazilian patients is similar to other populations. Our study identified two mutations exclusively found in Brazilians and also shows, for the first time, loss of heterozygosity in tumor DNA from an acromegaly patient harboring the A299V Our findings corroborate previous observations that screening should be performed in young patients with SPA.
芳烃受体相互作用蛋白（）基因突变（）是散发性垂体腺瘤（SPA）中最常见的种系突变。我们的目的是评估巴西年轻SPA患者中的突变频率。2013年至2016年期间，我们在一个单一的转诊中心进行了一项观察性队列研究。对132例诊断为40岁及以下的大腺瘤SPA患者或18岁及以下诊断为任何大小腺瘤的患者进行了筛查。还分析了12个肿瘤样本。对白细胞DNA和肿瘤组织DNA的整个编码区进行测序，以评估突变情况。132例患者中有11例（8.3%）发生了突变，其中生长激素瘤9/74例（12%），催乳素瘤1/38例（2.6%），促肾上腺皮质激素瘤1/10例（10%），无功能性腺瘤未发现突变。在儿科患者（≤18岁）中，突变频率为13.3%（2/15）。在5例巨人症患者中，有2例发生了突变，均为截短突变。Y268突变在巴西患者中已有报道，K273Rfs30突变是我们患者中的一个新突变。在12个肿瘤样本中未发现体细胞突变。一名肢端肥大症患者的肿瘤样本携带A299V突变，显示杂合性缺失。总之，巴西SPA患者中的突变频率与其他人群相似。我们的研究发现了两个仅在巴西人中发现的突变，并且首次显示了一名携带A299V突变的肢端肥大症患者肿瘤DNA中的杂合性缺失。我们的发现证实了之前的观察结果，即应对年轻的SPA患者进行筛查。
