南方科技大学知识苑(SUSTech KC): Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer

题名	Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer
作者	Zhang, Wei ; Lin, Shuhuang ; Wang, Zhuo; Zhang, Wenyong; Xing, Mingzhao
通讯作者	Xing, Mingzhao
发表日期	2024-05-01
DOI	10.1210/clinem/dgae327
发表期刊	JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 影响因子和分区
ISSN	0021-972X
EISSN	1945-7197
摘要	Context The role of RET/PTC rearrangement in the clinical outcomes of papillary thyroid cancer (PTC) is controversial and remains to be clearly undefined.Objective This work aimed to investigate the role of coexisting RET/PTC rearrangement and TERT promoter mutation in the prognosis and therapeutic targeting in PTC.Methods A total of 669 PTC patients with complete clinical follow-up and genetic data were pooled from thyroid cancer data sets TCGA-THCA, MSK-MetTropism, and MSK-IMPACT, from whom 163 patients (112 women and 47 men, 4 unknown) with wild-type (WT) BRAF/RAS were identified, with a median age (interquartile range [IQR]) of 46.00 (33.00-61.00) years and a median follow-up time (IQR) of 16.13 (8.09-27.91) months for comparative genotype cohort analysis of mortality.Results There was a significant concurrence index between RET/PTC and TERT promoter mutations, being 2.040 (95% CI, 1.110-3.747; P = .023). Mortality occurred in 5 of 100 (5%) patients harboring neither mutation, 2 of 18 (11.1%) patients harboring a TERT promoter mutation alone, 0 of 31 (0%) patients harboring a RET/PTC alone, and 7 of 14 (50%) patients harboring both genetic alterations, corresponding to hazard ratios (95% CI) of 1 (reference), 2.469 (0.405-14.022), 3.296e-09 (0-inf), and 9.019 (2.635-30.870), respectively, which remained essentially unchanged after adjustment for patient race, sex, and age. Similar results were observed with BRAF/RAS and TERT promoter mutations. Mechanistically, RET/PTC used the MAP kinase pathway to upregulate the mutated TERT, but not the WT TERT, and, correspondingly, targeting RET and MEK could suppress mutated TERT but not the WT TERT.Conclusion Coexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.
关键词	RET/PTC TERT promoter mutation thyroid cancer mortality prognostic biomarker
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	第一 ; 通讯
WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:001248997500001
出版者	ENDOCRINE SOC
ESI学科分类	CLINICAL MEDICINE
来源库	Web of Science
引用统计	被引频次[WOS]：2
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/787830
专题	南方科技大学医学院
作者单位	Southern Univ Sci & Technol, Thyroid Res Inst, Sch Med, 1088 Xueyuan Ave, Shenzhen 518055, Guangdong, Peoples R China
第一作者单位	南方科技大学医学院
通讯作者单位	南方科技大学医学院
第一作者的第一单位	南方科技大学医学院
推荐引用方式 GB/T 7714	Zhang, Wei,Lin, Shuhuang,Wang, Zhuo,et al. Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2024.
APA	Zhang, Wei,Lin, Shuhuang,Wang, Zhuo,Zhang, Wenyong,&Xing, Mingzhao.(2024).Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM.
MLA	Zhang, Wei,et al."Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2024).