Borowczyk Martyna, Szczepanek-Parulska Ewelina, Dębicki Szymon, Budny Bartłomiej, Janicka-Jedyńska Małgorzata, Gil Lidia, Verburg Frederik A, Filipowicz Dorota, Wrotkowska Elżbieta, Majchrzycka Blanka, Marszałek Andrzej, Ziemnicka Katarzyna, Ruchała Marek
Department of Endocrinology, Metabolism and Internal Diseases, Poznań University of Medical Sciences, Przybyszewskiego Street, 49, Poznan, 60-355, Poland.
Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland.
Ther Adv Med Oncol. 2020 Mar 4;12:1758835920907534. doi: 10.1177/1758835920907534. eCollection 2020.
Conventional treatments for follicular thyroid cancer (FTC) can be ineffective, leading to poor prognosis. The aim of this study was to identify mutations associated with FTC that would serve as novel molecular markers of the disease and its outcome and could potentially identify new therapeutic targets.
mutations were first detected in a 29-year-old White female diagnosed with metastasized, treatment-refractory FTC. Analyses of mutational status through next-generation sequencing of formalin-fixed, paraffin-embedded FTC specimens were subsequently performed in 35 randomly selected patients diagnosed with FTC.
mutations were found in 69% of patients. mutation-positive patients were significantly older than those that were mutation-negative [median age at diagnosis 54 (36-82) 45 (27-58) ( = 0.023)]. Patients over 60 years were 23 times more likely to be mutation-positive ( = 0.006). However, the number of mutations did not correlate with age (-Pearson: -0.244, -value: 0.25). A total of 26 mutations were identified in the gene with 2-16 mutations in each mutation-positive patient (mean: 5.6 mutations/patient). Tyrosine kinase domain (TKD) mutations in the gene were detected in 58% of mutation-positive patients. All mutation-positive patients with a disease stage of pT2N1 or worse harbored at least one mutation in the TKD of .
There is a wide spectrum and high frequency of mutations in FTC. The precise role of mutations in the genesis of FTC, as well as its potential role as a therapeutic target, requires further investigation.
滤泡性甲状腺癌（FTC）的传统治疗可能无效，导致预后不良。本研究的目的是鉴定与FTC相关的突变，这些突变可作为该疾病及其预后的新型分子标志物，并有可能确定新的治疗靶点。
首先在一名29岁被诊断为转移性、治疗难治性FTC的白人女性中检测到突变。随后，对35例随机选择的被诊断为FTC的患者，通过对福尔马林固定、石蜡包埋的FTC标本进行二代测序来分析突变状态。
69%的患者中发现了突变。突变阳性患者的年龄显著大于突变阴性患者[诊断时的中位年龄54（36 - 82）对45（27 - 58）（P = 0.023）]。60岁以上的患者突变阳性的可能性高23倍（P = 0.006）。然而，突变数量与年龄无关（皮尔逊相关系数：-0.244，P值：0.25）。在该基因中总共鉴定出26个突变，每个突变阳性患者有2 - 16个突变（平均：5.6个突变/患者）。58%的突变阳性患者检测到该基因的酪氨酸激酶结构域（TKD）突变。所有疾病分期为pT2N1或更差的突变阳性患者在该基因的TKD中至少有一个突变。
FTC中存在广泛的、高频的突变。突变在FTC发生中的精确作用及其作为治疗靶点的潜在作用需要进一步研究。
