Estrada-Flórez Ana P, Bohórquez Mabel E, Vélez Alejandro, Duque Carlos S, Donado Jorge H, Mateus Gilbert, Panqueba-Tarazona Cesar, Polanco-Echeverry Guadalupe, Sahasrabudhe Ruta, Echeverry Magdalena, Carvajal-Carmona Luis G
Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, California, USA.
Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultad de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Tolima, Colombia.
Endocr Connect. 2019 Sep;8(9):1310-1317. doi: 10.1530/EC-19-0376.
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 × 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 genotypes. 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.
乳头状甲状腺癌(PTC)是美国拉丁裔和哥伦比亚女性中第二常见的确诊恶性肿瘤。对非拉丁裔的研究表明,BRAF和TERT突变是PTC的预后标志物。本研究旨在确定来自哥伦比亚的PTC拉丁裔患者中BRAF和TERT突变的患病率及其临床关联。我们通过一项多中心研究,分析了141例患者(75例经典型PTC,CVPTC;66例滤泡型PTC,FVPTC)肿瘤DNA中BRAF(V600E)和TERT启动子(C228T、C250T)的突变情况。采用Fisher精确检验评估突变与临床变量之间的关联。用Kaplan-Meier曲线评估生存率。双突变肿瘤(BRAF+/TERT+,n = 14例患者)在CVPTC中更为常见(P = 0.02)。与无突变患者(n = 48)相比,双突变在肿瘤较大(P = 0.03)、有淋巴结转移(P = 0.01)、甲状腺外侵犯(P = 0.03)和晚期(P = 6.0×10⁻⁵)的患者中更为常见。在老年患者中,TERT突变更频繁(野生型TERT的平均年龄为45岁,突变型为51岁,P = 0.04),生存率更低(HR = 1.20;P = 0.017);然而,鉴于样本量较小,不同基因型之间生存率的降低无统计学意义。与美国白人已发表的数据比较显示,哥伦比亚患者严重病理特征和双突变肿瘤的患病率更高(分别为10%和6%,P = 0.001)。两种癌基因的突变在来自哥伦比亚的拉丁裔中显示出预后关联。我们的研究对于推进拉丁裔PTC精准医学很重要,并重复了该人群中BRAF和TERT之间先前的预后关联。