恶性肿瘤复发与p53热点突变体的相关性研究
网络出版日期: 2016-08-31
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
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 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
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。
王焕彬 许杰 . 恶性肿瘤复发与p53热点突变体的相关性研究[J]. 上海交通大学学报(医学版), 2016 , 36(8) : 1121 . DOI: 10.3969/j.issn.1674-8115.2016.08.003
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
/
〈 |
|
〉 |