首页 | 本学科首页   官方微博 | 高级检索  
     


Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis
Authors:Xiabin Lan  Hua Bao  Xinyang Ge  Jun Cao  Xiaojun Fan  Qihong Zhang  Kaihua Liu  Xian Zhang  Zhuo Tan  Chuanming Zheng  Ao Wang  Chao Chen  Xin Zhu  Jiafeng Wang  Jiajie Xu  Xuhang Zhu  Xue Wu  Xiaonan Wang  Yang Shao  Minghua Ge
Abstract:Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, with a relatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, it significantly decreases the survival of PTC patients. The molecular mechanisms of DM in PTC have not been systematically studied. We performed whole exome sequencing and GeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched white blood cell samples from 20 PTC with DM and 46 PTC without DM. We identified somatic mutations, gene fusions and copy number alterations and analyzed their relationships with DM of PTC. BRAF‐V600E was identified in 73% of PTC, followed by RET fusions (14%) in a mutually exclusive manner (P < 0.0001). We found that gene fusions (RET, ALK or NTRK1) (P < 0.01) and chromosome 22q loss (P < 0.01) were independently associated with DM in both univariate and multivariate analyses. A nomogram model consisting of chromosome 22q loss, gene fusions and three clinical variables was built for predicting DM in PTC (C‐index = 0.89). The plasma circulating tumor DNA (ctDNA) detection rate in PTC was only 38.9%; however, it was significantly associated with the metastatic status (P = 0.04), tumor size (P = 0.001) and invasiveness (P = 0.01). In conclusion, gene fusions and chromosome 22q loss were independently associated with DM in PTC and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate was low in non–DM PTC but significantly higher in PTC with DM.
Keywords:circulating tumor DNA  distant metastasis  mutation  nomogram  papillary thyroid carcinoma
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号