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P53是一系列肿瘤抑制蛋白（抑癌蛋白）同源异构蛋白的统称，1979年由于凝胶电泳测得其分子量约为53kDa，由肿瘤抑制基因（抑癌基因）TP53编码，是最早发现的肿瘤抑制基因编码蛋白之一，能够调节细胞分裂周期，从而避免细胞癌变发生，并保持基因组的稳定性，避免或减少突变的发生，大约有一半的人类癌症由于TP53基因突变失活引起，故被称为基因组守护者。该基因致病突变携带者与未携带者相比，癌症发生风险大约高100倍。不过，中国乳腺癌女性TP53突变的临床病理特征及其预后影响尚不明确。 基因组守护者TP53 2020年5月15日，世界华人胸外科学会官方期刊《胸部癌症》在线发表广东省医学科学院广东省人民医院李学瑞、陈小清、温灵珠、王钰雷、陈博、薛允莲、郭丽萍、廖宁等学者的研究报告，探讨了中国乳腺癌女性TP53突变的临床病理特征及其预后影响。 该单中心队列回顾研究对2017年6月～2018年9月广东省人民医院确诊的411例乳腺浸润癌治疗前患者TP53突变检测结果和临床病理特征进行回顾分析，并且将广东省人民医院患者队列数据与国际乳腺癌分子分类联盟METABRIC患者队列数据进行比较分析。 结果，广东省人民医院患者队列与METABRIC患者队列相比，TP53突变的发生比例显著较高（51.3%比34.4%，P<0.01）。 广东省人民医院患者队列77.8%的突变位于TP53外显子5～8保守区，其中错义突变112个，主要集中于DNA结合区。广东省人民医院患者队列检出最多的两个突变位点为R273C/H（11例）和R248Q/W（10例）。 逻辑回归多因素分析表明，广东省人民医院患者队列TP53突变比例较高的显著相关因素（P<0.001）包括：
此外，该研究结合分子分型和Ki-67，建立了预测TP53突变的接受者操作特征模型，曲线下面积高达0.846。 因此，该研究结果表明，中国女性乳腺癌患者人群与METABRIC患者人群相比，TP53突变检出比例显著较高。相关因素分析表明，乳腺癌患者TP53突变与激素受体阴性和HER2阳性、较高的Ki-67和组织学分级密切相关。 相关链接 Thorac Cancer. 2020 May 15. [Epub ahead of print] Impact of TP53 mutations in breast cancer: Clinicopathological features and prognosisImpact of TP53 mutations in breast CA. Li X, Chen X, Wen L, Wang Y, Chen B, Xue Y, Guo L, Liao N. Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China. BACKGROUND: TP53 is a crucial tumor suppressor gene. However, the mutation pattern of TP53 in Chinese patients with breast cancer has not yet been determined. METHODS: A total of 411 untreated patients with invasive breast cancer diagnosed at Guangdong Provincial People's Hospital (GDPH) between June 2017 to September 2018 were recruited into the study. Mutational alterations in TP53 were detected and correlations between TP53 mutations and clinicopathological features analyzed. Comparative analysis of the data in the GDPH cohort with those in the METABRIC cohort were carried out. RESULTS: A significantly higher rate of TP53 mutations was detected in the GDPH cohort (51.3%) compared with the METABRIC cohort (34.4%) (P<0.01). In the GDPH cohort, 77.8% of the mutations were located in the conserved areas across exons 5-8 of TP53; among these, 112 were identified as missense mutations and mainly clustered in the DNA-binding region. R273C/H (n = 11) and R248Q/W (n = 10) were two of the most common mutation sites of TP53 detected in the cohort of GDPH patients. Logistic regression multivariate analysis showed that histological grade III, ki-67> = 25%, HR- and Her2+ in breast cancer had higher mutation probability of TP53 (P <0.001 in the GDPH cohort). Furthermore, receiver operating characteristic (ROC) model combining molecular typing and Ki-67 was established to predict the mutation of TP53, and the AUC was 0.846. CONCLUSIONS: A significantly higher rate of TP53 mutation was detected in the Chinese cohort compared with the METABRIC. Correlation analysis revealed a significant association of TP53 mutation with HR- and HER2+, higher Ki-67 and histological grade in breast cancer patients. KEYWORDS: TP53; Breast cancer; genomic mutation; next-generation sequencing PMID: 32412177 DOI: 10.1111/1759-7714.13467
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