Guo Wei, Huang Junwei, Shi Taiping, Duan Hanyuan, Chen Xiaohong, Huang Zhigang
Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
BGI (Beijing Genomics Institution), BGI-Shenzhen, Shenzhen, China.
Front Oncol. 2022 Jul 5;12:816897. doi: 10.3389/fonc.2022.816897. eCollection 2022.
Papillary Thyroid Carcinoma (PTC) is one of the most commonly diagnosed cancer types in China, characterized by its early age at diagnosis and high 25-year survival rate. Distinct mutational patterns in PTC have been linked to activation of the mitogen-activated protein kinase (MAPK) signaling pathway. To explore the clinical significance of genomic variation patterns in Chinese patients with thyroid carcinoma, we investigated the genomic variants in 83 PTC cases with complete clinical records. The mutational patterns were evaluated using a 688-gene panel which covered known driver genes in PTC tumorigenesis, and featured genetic markers in various PTC-related pathways. We evaluated the relationship between mutational landscape and various clinical information in PTC patients with lateral lymph node metastasis. BRAF V600E was the most common mutation. Mutations in NF1, CDC27, PMS2 and PPP4R2 were more common in men, and mutations in NF1, PMS2 and TERT were related to lateral lymph node metastasis. According to the clustering of mutational patterns, we show that the underline driving mechanisms in lateral lymph node metastasis can be divided into two major groups (BRAF-TERT pathway, and NF1-PMS2 pathway). When combined with the TERT mutations, the BRAF mutation group was prone to lateral lymph node metastasis, particularly in elderly women. The NF1 mutations usually co-existed with PMS2 mutations, and this group included more men and young patients who had a high tumor mutational burden and lateral lymph node metastasis rate.
甲状腺乳头状癌（PTC）是中国最常被诊断出的癌症类型之一，其特点是诊断年龄早且25年生存率高。PTC中独特的突变模式与丝裂原活化蛋白激酶（MAPK）信号通路的激活有关。为了探究中国甲状腺癌患者基因组变异模式的临床意义，我们调查了83例有完整临床记录的PTC病例的基因组变异。使用一个包含PTC肿瘤发生中已知驱动基因且涵盖各种PTC相关通路中基因标记的688基因panel评估突变模式。我们评估了伴有侧方淋巴结转移的PTC患者的突变图谱与各种临床信息之间的关系。BRAF V600E是最常见的突变。NF1、CDC27、PMS2和PPP4R2的突变在男性中更常见，NF1、PMS2和TERT的突变与侧方淋巴结转移有关。根据突变模式的聚类分析，我们发现侧方淋巴结转移的潜在驱动机制可分为两大组（BRAF-TERT通路和NF1-PMS2通路）。当与TERT突变结合时，BRAF突变组更容易发生侧方淋巴结转移，尤其是老年女性。NF1突变通常与PMS2突变共存，该组男性和年轻患者较多，肿瘤突变负荷高且侧方淋巴结转移率高。
