BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry
BRAF and TERT mutations in papillary thyroid cancer patients of Latino ancestry
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DOI：
10.1530/ec-19-0376
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发表时间：
2019-09-01
影响因子：
2.9
通讯作者：
Carvajal-Carmona, Luis G.
中科院分区：
文献类型：
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作者：
Estrada-Florez, Ana P.;Bohorquez, Mabel E.;Carvajal-Carmona, Luis G.
甲状腺乳头状癌 (PTC) 是美国拉丁裔和哥伦比亚女性中第二常见的恶性肿瘤。针对非拉丁裔的研究表明 BRAF 和 TERT 突变是 PTC 预后标志物。本研究旨在确定哥伦比亚 PTC 拉丁裔患者中 BRAF 和 TERT 突变的患病率和临床关联。我们分析了通过多中心研究招募的 141 名患者（75 名经典变异型 PTC、CVPTC；66 名滤泡变异型 PTC、FVPTC）肿瘤 DNA 中 BRAF (V600E) 和 TERT 启动子（C228T、C250T）的突变。通过费舍尔精确检验评估突变与临床变量之间的关联。用卡普兰-迈耶图评估生存率。双突变肿瘤（BRAF+/TERT+，n = 14 例患者）在 CVPTC 中更为常见（P = 0.02）。相对于无突变的患者（n = 48），双突变在肿瘤较大（P = 0.03）、淋巴结转移（P = 0.01）、甲状腺外扩展（P = 0.03）和晚期（P = 6.0 x 10(-5)）的患者中更为常见。在老年患者中，TERT 突变更为频繁（平均年龄 51 岁，野生型 TERT 为 45 岁，P = 0.04），生存率较低（HR = 1.20；P = 0.017）；然而，由于样本量较小，基因类型之间的生存率下降并不具有静态显着性。与美国白人中已发表的数据进行比较显示，哥伦比亚患者的严重病理特征和双突变肿瘤的患病率较高（10% vs 6%，P = 0.001）。两种癌基因的突变都显示出哥伦比亚拉丁裔的预后相关性。我们的研究对于推进拉丁裔 PTC 精准医学非常重要，并在该人群中复制了 BRAF 和 TERT 之间先前的预后关联。
Papillary thyroid cancer (PTC) is the second most commonly diagnosed malignancy in U.S. Latinas and in Colombian women. Studies in non-Latinos indicate that BRAF and TERT mutations are PTC prognostic markers. This study aimed to determine the prevalence and clinical associations of BRAF and TERT mutations in PTC Latino patients from Colombia. We analyzed mutations of BRAF (V600E) and TERT promoter (C228T, C250T) in tumor DNA from 141 patients (75 with classical variant PTC, CVPTC; 66 with follicular variant PTC, FVPTC) recruited through a multi-center study. Associations between mutations and clinical variables were evaluated with Fisher exact tests. Survival was evaluated with Kaplan-Meier plots. Double-mutant tumors (BRAF+/TERT+, n = 14 patients) were more common in CVPTC (P = 0.02). Relative to patients without mutations (n = 48), double mutations were more common in patients with large tumors (P = 0.03), lymph node metastasis (P = 0.01), extra-thyroid extension (P = 0.03), and advanced stage (P = 6.0 x 10(-5)). In older patients, TERT mutations were more frequent (mean age 51 years vs 45 years for wild type TERT, P = 0.04) and survival was lower (HR = 1.20; P = 0.017); however, given the small sample size, the decrease in survival was not statically significant between geno types. Comparisons with published data in US whites revealed that Colombian patients had a higher prevalence of severe pathological features and of double-mutant tumors (10 vs 6%, P = 0.001). Mutations in both oncogenes show prognostic associations in Latinos from Colombia. Our study is important to advance Latino PTC precision medicine and replicates previous prognostic associations between BRAF and TERT in this population.