上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2016, Vol. 36 ›› Issue (08): 1121-.doi: 10.3969/j.issn.1674-8115.2016.08.003

• 论著（基础研究） • 上一篇    下一篇

恶性肿瘤复发与p53热点突变体的相关性研究

王焕彬 许杰   

  1. 上海交通大学 医学院附属仁济医院消化科，癌基因与相关基因国家重点实验室，卫生部内科消化重点实验室，上海市肿瘤研究所，上海市消化疾病研究所，上海 200001
  • 出版日期:2016-08-29 发布日期:2016-08-31
  • 通讯作者: 许 杰，电子信箱：jiexu@sjtu.edu.cn。
  • 作者简介:王焕彬（1989—），女，硕士生；电子信箱：wanghuanbin2010@163.com。
  • 基金资助:

    国家自然科学基金（81572326，81322036，30971330，31371420，81320108024， 81000861，81421001，81272383）；中组部青年拔尖人才计划（ZTZ2015-48）；国家科技支撑计划（2015BAI13B07）；上海市教育委员会高原高峰学科建设计划（20152514）

Association between cancer relapse and p53 hotspot mutations

WANG Huan-bin, XU Jie   

  1. Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai 200001, China

  • Online:2016-08-29 Published:2016-08-31
  • Supported by:

    National Natural Science Foundation of China, 81572326, 81322036, 30971330, 31371420, 81320108024, 81000861, 81421001, 81272383; Top-Notch Young Talents Program of China, ZTZ2015-48; National Key Technology Support Program, 2015BAI13B07; Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support, 20152514

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摘要：

目的·探讨肿瘤复发与p53不同位点突变体之间的相关性。方法·癌症基因组计划（TCGA）和纪念斯隆-凯特琳癌症中心（MSKCC）中的肿瘤患者按照携带的p53突变体类型进行分类，并比较肿瘤手术治疗后复发时间的差异。结果·位于第248和282氨基酸位点的p53错义突变体与肿瘤复发时间的缩短显著相关（P<0.05，HR>2）。虽然位于175、245和273位点的热点突变体具有增加的风险比，但差异并无统计学意义。当相同类别的突变被归为一组时，热点突变体（而不是所有错义突变体）与更短的复发时间相关。移码突变体与无义突变体具有基本相当的肿瘤复发时间。结论·并非所有p53热点突变体都与肿瘤复发时间的缩短相关，p53的各种热点突变应该作为不同的肿瘤标记物加以区别对待。

关键词: 癌症复发, p53突变, 功能获得效应

Abstract:

Objective · To investigate the association between different p53 mutations and cancer relapse. Methods · Cancer patients in The Cancer Genome Atlas (TCGA) and MSKCC bladder cancer dataset were stratified according to TP53 genotypes and compared for the relapse-free survival (RFS). Results · Missense mutations at R248 and R282 positions were significantly associated with shorter RFS (P<0.05, HR>2). Although increased hazard ratios were also found for hotspot mutations at R175, G245, and R273 positions, no statistical significance was reached. When mutations of the same type were considered as a cluster, hotspot mutations (but not all missense mutations) were associated with shorter RFS. Frameshift mutations and nonsense mutations had similar effects on RFS. Conclusion · Not all p53 hotspot mutations are associated with shorter RFS, suggesting that p53 hotspot mutations should be differentially treated as different tumor markers.
 

Key words: cancer relapse, mutant p53, gain of function