Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis

doi:10.1111/cas.14389

	Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis
	Lan, Xiabin 7,8; Bao, Hua 2; Ge, Xinyang 3,8; Cao, Jun 8; Fan, Xiaojun 2; Zhang, Qihong 4; Liu, Kaihua 1; Zhang, Xian 1; Tan, Zhuo 7,8; Zheng, Chuanming 5
刊名	CANCER SCIENCE
	2020-04-16
关键词	circulating tumor DNA distant metastasis mutation nomogram papillary thyroid carcinoma
ISSN号	1347-9032
DOI	10.1111/cas.14389
通讯作者	Ge, Minghua(gemingh@163.com)
英文摘要	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.
资助项目	National Natural Science Foundation of China[81702645] ; National Natural Science Foundation of China[81702653] ; National Natural Science Foundation of China[81602349] ; National Natural Science Foundation of China[81802674] ; National Natural Science Foundation of China[81672642] ; National Natural Science Foundation of China[81872170] ; China Postdoctoral Science Foundation[2018M642488] ; Medical and Health Research Program of Zhejiang Province[2016KYA054] ; Zhejiang Province Natural Science Foundation of China[LY17H070003] ; Zhejiang Cancer Hospital Young Talent Program
WOS关键词	FREQUENT ALLELIC LOSSES ; TERT PROMOTER MUTATIONS ; BRAF V600E MUTATION ; CANCER STATISTICS ; CHROMOSOME 22Q ; ASSOCIATION ; DNA ; PREVALENCE ; SURVIVAL ; OUTCOMES
WOS研究方向	Oncology
语种	英语
出版者	WILEY
WOS记录号	WOS:000526882300001
资助机构	National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; Medical and Health Research Program of Zhejiang Province ; Zhejiang Province Natural Science Foundation of China ; Zhejiang Cancer Hospital Young Talent Program
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103699]
专题	中国科学院合肥物质科学研究院
通讯作者	Ge, Minghua
作者单位	1.Nanjing Geneseeq Technol Inc, Nanjing, Peoples R China 2.Geneseeq Technol, Translat Med Res Inst, Toronto, ON, Canada 3.Heartland Christian Sch, Columbiana, OH USA 4.Zhejiang Chinese Med Univ, Hangzhou, Zhejiang, Peoples R China 5.Hangzhou Med Coll, Dept Head Neck & Thyroid Surg, Zhejiang Prov Peoples Hosp, Peoples Hosp, 158,Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China 6.Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China 7.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Head & Neck Surg, Hangzhou, Zhejiang, Peoples R China 8.Chinese Acad Sci, Inst Canc & Basic Med, Key Lab Head & Neck Canc Translat Res Zhejiang Pr, Hangzhou, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Lan, Xiabin,Bao, Hua,Ge, Xinyang,et al. Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis[J]. CANCER SCIENCE,2020.
APA	Lan, Xiabin.,Bao, Hua.,Ge, Xinyang.,Cao, Jun.,Fan, Xiaojun.,...&Ge, Minghua.(2020).Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis.CANCER SCIENCE.
MLA	Lan, Xiabin,et al."Genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis".CANCER SCIENCE (2020).