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The clinicopathological and prognostic significance of TP53 alteration in K27M mutated gliomas: an individual-participant data meta-analysis

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Abstract

This study aimed to investigate the impact of TP53 alteration on survival and clinicopathological features of glioma patients with H3K27M mutations. An individual-participant-data (IPD) meta-analysis was performed to investigate the impact of TP53 alteration on survival and clinicopathological features of patients with H3K27M mutations. Three hundred thirty-one individual records from 12 eligible glioma studies involving the H3K27M mutation were finally included in our meta-analysis, and a pooled hazard ratio (HR) of 1.53 (95%CI, 1.10–2.11; P = 0.01) indicated that TP53 alterations were associated with a shorter overall survival. The pooled odds ratios (ORs) indicated that TP53 alterations were significantly associated with the age at diagnosis ≥ 7 years (OR = 1.97, 95%CI = 1.15–3.38, P = 0.01), the status of histone H3.3 mutations (OR = 9.15, 95%CI = 4.18–20.06, P < 0.00001), and high WHO grade histology (III + IV) (OR = 2.70, 95%CI = 1.33–5.48, P = 0.006). However, no association was found between TP53 alterations and gender or tumor location. This IPD meta-analysis suggests that TP53 alteration is a valuable predictor for the prognosis of patients with H3K27M mutated gliomas. TP53 alteration may be used for identifying a subset of patients who potentially benefit from targeted reactivation of TP53 activity.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81572474), Natural Science Foundation of Beijing (7152098), and the Science and Technology Development Fund Project of Traditional Chinese Medicine of Beijing (JJ2015-14).

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Authors and Affiliations

  1. Core Laboratory for Clinical Medical Research, Beijing Tian Tan Hospital, Capital Medical University, 6 Tiantan Xili, Beijing, 100050, China

    Chengya Dong & Qi Li

  2. College of Biological Sciences and Technology, Beijing Forestry University, 35 Tsinghua East Road, Beijing, 100083, China

    Zhengrong Yuan

  3. Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun Dongjie Chaoyang District, Beijing, 100015, People’s Republic of China

    Yajie Wang

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  1. Chengya Dong
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Dong, C., Yuan, Z., Li, Q. et al. The clinicopathological and prognostic significance of TP53 alteration in K27M mutated gliomas: an individual-participant data meta-analysis. Neurol Sci 39, 1191–1201 (2018). https://doi.org/10.1007/s10072-018-3407-1

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