Department of Nuclear Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, and Hunan Cancer Hospital, Changsha, 410013, China.
Shenzhen Cheerland Biotechnology Co., Ltd, Shenzhen, 518055, China.
Diagn Pathol. 2020 May 11;15(1):49. doi: 10.1186/s13000-020-00962-8.
The objective of this study was to investigate genetic variations and the relationships between these genetic variations and clinicopathological features of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population.
One hundred sixty-eight patients of high-recurrence risk papillary thyroid carcinoma were recruited for this study from 2017 to 2018. Formalin-fixed paraffin-embedded tissue and the data of clinicopathological characteristics were all collected and analyzed from these patients. We used next-generation sequencing technology to investigate the targeted gene mutations and gene fusions of the pathology specimens.
The frequency of candidate tumor driver gene mutation was 85.1% in 143 patients, including BRAF V600E mutation in 119 patients(70.8%), RET fusion in 13 patients(7.7%), TERT promoter mutations in 11 patients(6.5%), RAS (HRAS, NRAS, KRAS) gene mutations in 10 patients(6.0%), and other mutations involving TP53, PIK3CA, AKT1, PTEN and NTRK1. Concomitant presence of more than two genetic aberrations was seen in 27 patients (16.1%). Our study showed that BRAF V600E mutation is highly correlated with conventional PTC (p < 0.001), BRAF V600E and TERT promoter mutation duet was associated with older patient age (> 45, p = 0.003) and higher disease stage of III or IV (p = 0.002). RAS gene and BRAF V600E co-mutations were only seen in multifocal PTC (p = 0.015).
In our high-recurrence risk PTC cohort, most patients had more than one driver gene aberration. Coexistence of BRAF V600E with TERT promoter mutations or with RAS mutations were significantly correlated with worse clinicopathological characteristics.
本研究旨在探讨中国南方人群高复发风险甲状腺乳头状癌的遗传变异及其与临床病理特征的关系。
本研究纳入了 2017 年至 2018 年期间的 168 例高复发风险甲状腺乳头状癌患者。收集并分析了这些患者的福尔马林固定石蜡包埋组织和临床病理特征数据。我们使用下一代测序技术对病理标本的候选肿瘤驱动基因突变和基因融合进行了研究。
在 143 例患者中，候选肿瘤驱动基因突变的频率为 85.1%，包括 119 例（70.8%）患者的 BRAF V600E 突变、13 例（7.7%）患者的 RET 融合、11 例（6.5%）患者的 TERT 启动子突变、10 例（6.0%）患者的 RAS（HRAS、NRAS、KRAS）基因突变以及涉及 TP53、PIK3CA、AKT1、PTEN 和 NTRK1 的其他突变。27 例（16.1%）患者同时存在两种以上遗传异常。本研究显示，BRAF V600E 突变与经典型 PTC 高度相关（p<0.001），BRAF V600E 和 TERT 启动子突变双突变与患者年龄较大（>45 岁，p=0.003）和疾病分期较高（III 或 IV 期，p=0.002）相关。RAS 基因突变与 BRAF V600E 共突变仅见于多灶性 PTC（p=0.015）。
在我们的高复发风险 PTC 队列中，大多数患者存在不止一种驱动基因突变。BRAF V600E 与 TERT 启动子突变或与 RAS 突变共存与更差的临床病理特征显著相关。
