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Non-disruptive mutation in TP53 DNA-binding domain is a beneficial factor of esophageal squamous cell carcinoma

文献类型：期刊论文

作者Huang, Minran3,4,5,6; Jin, Jiaoyue4,5,6; Zhang, Fanrong1,4,7; Wu, Yingxue4,5,6; Xu, Chenyang4,5,6; Ying, Lisha2,4; Su, Dan4,5,6
刊名ANNALS OF TRANSLATIONAL MEDICINE
出版日期2020-03-01
卷号8
关键词Esophageal squamous cell carcinoma (ESCC) TP53 mutation next-generation sequencing (NGS) prognosis
ISSN号2305-5839
DOI10.21037/atm.2020.02.142
通讯作者Su, Dan(sudan@zjcc.org.cn)
英文摘要Background: TP53 is frequently altered in esophageal squamous cell carcinoma (ESCC). However, the landscape of TP53 mutation and its effects on patients remain controversial. Methods: Somatic mutations of TP53 in 161 patients with resectable ESCC were identified by next-generation sequencing (NGS) and verified by immunohistochemistry (IHC). Patients were stratified into seven TP53 mutations, and depending on the extent of the effect on the encoded protein, it was divided into "disruptive" and "non-disruptive" types. The association of TP53 mutation with clinicopathological properties and disease outcome was investigated. Results: TP53 mutations were discovered in 85.7% patients, of which 68.9% carried mutations in the DNA-binding domain (DBD). A total of 47.8% and 37.9% patients had disruptive and non-disruptive TP53 mutations, respectively. Most patients carried only one TP53 mutation, but 15.5% had double mutations. TP53 mutations were dominant in exons 5 to 8. Missense mutation was the most frequent (97/163, 59.5%), and the top five frequently occurring variations included R273X, Y220X, H193, H179X, and R175H. Multivariable analysis revealed non-disruptive mutation in TP53 DBD as the independent prognostic predictor for progression-free survival (PFS) and overall survival (OS). The expression of p53 positively correlated with non-disruptive mutation in DBD. Patients with high p53 protein expression showed better outcomes. Conclusions: Non-disruptive mutation in TP53 DBD serves as an independent beneficial prognostic factor of prolonged survival in resectable ESCC.
WOS关键词GENE COPY NUMBER ; GAIN-OF-FUNCTION ; MUTANT P53 ; PROTEIN EXPRESSION ; MISSENSE MUTATIONS ; HUMAN CANCER ; SURVIVAL ; PREDICTION ; HEAD ; EGFR
资助项目National Natural Science Foundation of China[81472203] ; Major Science and Technology Plan of Zhejiang Medicine and Health - National Health Commission[WKJ-ZJ-1902]
WOS研究方向Oncology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:000522784900059
出版者AME PUBL CO
资助机构National Natural Science Foundation of China ; Major Science and Technology Plan of Zhejiang Medicine and Health - National Health Commission
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/103469]  
专题中国科学院合肥物质科学研究院
通讯作者Su, Dan
作者单位1.Univ Chinese Acad Sci, Canc Hosp, Dept Breast Surg, Hangzhou 310022, Peoples R China
2.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Peoples R China
3.Zhejiang Chinese Med Univ, Clin Med Coll 2, Dept Oncol, Hangzhou 310053, Peoples R China
4.Chinese Acad Sci, ICBM, Hangzhou, Peoples R China
5.Univ Chinese Acad Sci, Canc Hosp, Dept Pathol, Hangzhou 310022, Peoples R China
6.Zhejiang Canc Hosp, Dept Pathol, Hangzhou 310022, Peoples R China
7.Zhejiang Canc Hosp, Dept Breast Surg, Hangzhou 310022, Peoples R China
推荐引用方式
GB/T 7714		 Huang, Minran,Jin, Jiaoyue,Zhang, Fanrong,et al. Non-disruptive mutation in TP53 DNA-binding domain is a beneficial factor of esophageal squamous cell carcinoma[J]. ANNALS OF TRANSLATIONAL MEDICINE,2020,8.
APA Huang, Minran.,Jin, Jiaoyue.,Zhang, Fanrong.,Wu, Yingxue.,Xu, Chenyang.,...&Su, Dan.(2020).Non-disruptive mutation in TP53 DNA-binding domain is a beneficial factor of esophageal squamous cell carcinoma.ANNALS OF TRANSLATIONAL MEDICINE,8.
MLA Huang, Minran,et al."Non-disruptive mutation in TP53 DNA-binding domain is a beneficial factor of esophageal squamous cell carcinoma".ANNALS OF TRANSLATIONAL MEDICINE 8(2020).

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来源：合肥物质科学研究院

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