■近几十年来,中国甲状腺癌的发病率迅速上升。由于甲状腺癌的遗传特征在不同地理区域之间差异很大,中国人群中甲状腺癌的全面遗传景观是迫切需要的。
■我们回顾性纳入了2015年2月至2020年8月三个中国医疗中心的甲状腺癌患者。为了剖析这些患者的基因组特征,我们使用1,021个基因小组对其肿瘤组织进行了靶向下一代测序.
■共纳入458例中国甲状腺癌患者,包括由滤泡性甲状腺上皮细胞引起的四种恶性组织学亚型。在76.0%的患者中发现了BRAF驱动突变,其次是RET重排(7.6%)和RAS驱动突变(4.1%)。具有更多体细胞突变的肿瘤与更差的临床特征相关,包括诊断时年龄较大,肿瘤分化较少,肿瘤较大,淋巴结转移和远端转移。亚克隆BRAF突变发生在20%(6/30)的患者中,在低分化或间变性肿瘤中常见(33.3%[2/6]vs.4.2%[1/24],P=0.09)和远端转移者(50.0%[2/4]vs.8.7%[2/23],P=0.09)。具有TERT启动子突变的肿瘤具有明显更多的体细胞突变(平均:6.5vs.1.8,P<0.001)。此外,TERT启动子突变与淋巴结转移无关,但与诊断时的年龄和低分化或间变性肿瘤显著相关。不管他们的克隆结构如何。
■我们的研究结果揭示了中国人群甲状腺癌的分子发病机制和临床特征。体细胞突变的数量,TERT启动子突变,在甲状腺癌的危险分层中,应考虑BRAF突变的克隆结构.
The incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed.
We retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel.
A total of 458 Chinese patients with thyroid cancer were enrolled, including four malignant histological subtypes arising from follicular epithelial thyroid cells. BRAF driver mutations were identified in 76.0% of patients, followed by RET rearrangements (7.6%) and RAS driver mutations (4.1%). Tumors with more somatic mutations correlated with worse clinical characteristics, including older age at diagnosis, less differentiation of tumor, larger tumor size, lymph node metastasis and distal metastasis. Subclonal BRAF mutations occurred in 20% (6/30) of patients and were frequent in poorly differentiated or anaplastic tumors (33.3% [2/6] vs. 4.2% [1/24], P = 0.09) and those with distal metastasis (50.0% [2/4] vs. 8.7% [2/23], P = 0.09). Tumors with TERT promoter mutations had significantly more somatic mutations (average: 6.5 vs. 1.8, P < 0.001). Moreover, TERT promoter mutations were not associated with lymph node metastasis but significantly associated with older age at diagnosis and poorly differentiated or anaplastic tumors, regardless of their clonal architecture.
Our results shed light on the molecular pathogenesis and clinical characteristics of thyroid cancer in the Chinese population. The number of somatic mutations, TERT promoter mutations, and the clonal architecture of BRAF mutations should be considered in the risk stratification of thyroid cancer.