Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Liu,Yutao; Xu,Fang; Wang,Yubo; Wu,Qingchen; Wang,Buhai; Yao,Yanwen; Zhang,Yu; Han‑Zhang,Han; Ye,Junyi; Zhang,Lu; Mao,Xinru; Zhang,Zhe; Liu,Jing; Zhu,Liangjun; Guo,Renhua

doi:10.3892/ol.2019.10625

Mutations in exon 8 of TP53 are associated with shorter survival in patients with advanced lung cancer

Authors:
- Yutao Liu
- Fang Xu
- Yubo Wang
- Qingchen Wu
- Buhai Wang
- Yanwen Yao
- Yu Zhang
- Han Han‑Zhang
- Junyi Ye
- Lu Zhang
- Xinru Mao
- Zhe Zhang
- Jing Liu
- Liangjun Zhu
- Renhua Guo
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Affiliations: Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Thoracic Medicine, Hunan Cancer Center and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410006, P.R. China, Department of Respiratory Medicine, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China, Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China, Department of Medical Oncology, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, P.R. China, Department of Respiratory Medicine, Nanjing General Hospital of Nanjing Military Area Command, Nanjing, Jiangsu 210002, P.R. China, Department of Respiratory Medicine, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210029, P.R. China, Burning Rock Biotech, Guangzhou, Guangdong 510300, P.R. China, Department of Internal Medicine, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, P.R. China
Published online on: July 16, 2019 https://doi.org/10.3892/ol.2019.10625
Pages: 3159-3169
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Currently, in clinical settings, all TP53 mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for TP53 mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of TP53 mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture‑based ultra‑deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor‑naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all TP53 mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different TP53 mutation classification systems in a large cohort of patients with advanced lung cancer.

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