Pekova Barbora, Sykorova Vlasta, Mastnikova Karolina, Vaclavikova Eliska, Moravcova Jitka, Vlcek Petr, Lastuvka Petr, Taudy Milos, Katra Rami, Bavor Petr, Kodetova Daniela, Chovanec Martin, Drozenova Jana, Astl Jaromir, Hrabal Petr, Vcelak Josef, Bendlova Bela
Department of Molecular Endocrinology, Institute of Endocrinology, 11694 Prague, Czech Republic.
Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, 15006 Prague, Czech Republic.
Cancers (Basel). 2021 Apr 16;13(8):1932. doi: 10.3390/cancers13081932.
Chromosomal rearrangements of genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a , , , , or mutation were excluded from further analyses. fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of fusions were found, including , , , , , , and fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. -rearranged carcinomas showed a higher frequency of multifocality and aggressivity than -rearranged carcinomas. Tumor size, presence of metastases, positivity for the or fusion gene and a late mutation event ( or mutation) were determined as factors affecting patient prognosis. fusion genes are valuable diagnostic and prognostic markers.
基因的染色体重排是甲状腺癌(TC)中的致癌驱动突变。本研究旨在识别融合阳性甲状腺肿瘤,并将其与临床和病理数据相关联,确定其预后意义。该队列由989个不同的TC样本组成。根据检测到的突变对样本进行分类,那些α、β、γ、δ、ε或ζ突变呈阳性的样本被排除在进一步分析之外。对259例病例进行了RET融合基因检测,其中126例使用下一代测序。在846例乳头状甲状腺癌中有57例(6.7%)检测到RET融合基因,在10例低分化甲状腺癌中有2例(20.0%)检测到。共发现8种类型的RET融合,包括RET-PTC1、RET-PTC2、RET-PTC3、RET-PTC4、RET-PTC5、RET-PTC6、RET-PTC7和RET-PTC8。RET融合阳性癌与滤泡生长模式、慢性淋巴细胞性甲状腺炎和淋巴结转移相关。RET重排癌比NTRK1重排癌表现出更高的多灶性和侵袭性频率。肿瘤大小、转移情况、RET或NTRK1融合基因阳性以及晚期突变事件(α或β突变)被确定为影响患者预后的因素。RET融合基因是有价值的诊断和预后标志物。