恶性肿瘤复发与p53热点突变体的相关性研究
Association between cancer relapse and p53 hotspot mutations

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。
： 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