Chen Xu-Feng, He Cong, Yu Peng-Cheng, Ye Wei-Dong, Han Pei-Zheng, Hu Jia-Qian, Wang Yu-Long
1Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
Endocr Connect. 2024 Oct 9;13(11). doi: 10.1530/EC-24-0301. Print 2024 Oct 1.
Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022. Among the cohort, 2337 (82%) cases possess genetic alterations, including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%), and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF-positive papillary thyroid cancer (PTC) patients tend to have older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.
下一代测序(NGS)在识别基因改变方面对临床实践有很大益处。本研究旨在阐明中国人群甲状腺肿瘤的基因背景及其影响。回顾性收集并分析了2021年7月至2022年8月期间2844例个体甲状腺肿瘤样本的NGS数据及相应的临床病理特征(性别、年龄、肿瘤大小、甲状腺外侵犯、转移、多灶性和TNM分期)。在该队列中,2337例(82%)病例存在基因改变,包括BRAF(71%)、RAS(4%)、RET/PTC(4%)、TERT(3%)、RET(2.2%)和TP53(1.4%)。当细胞学检查辅以NGS时,术前诊断敏感性可从0.76显著提高到0.91。我们的结果表明,BRAF阳性的甲状腺乳头状癌(PTC)患者往往年龄较大、肿瘤较小、血管侵犯较少、肿瘤多灶性更常见,且颈部淋巴结转移率显著更高。RET基因密码子918和634处的突变与甲状腺髓样癌密切相关。然而,它并未表现出更具侵袭性的临床特征。TERT阳性患者更可能年龄较大,肿瘤较大、侵袭性更强且TNM分期更晚,提示预后不良。携带TERT、RET/PTC1和CHEK2突变的患者更容易发生侧方淋巴结转移。总之,NGS可以成为一种有用的工具,在甲状腺肿瘤的诊断和治疗过程中提供实用的基因证据。