Characteristics of <i>TP53</i> germline variants and their correlations with Li-Fraumeni syndrome or Li-Fraumeni-like syndrome in Chinese tumor patients

Panwen Tian; Xiaoyan Zhang; Sheng Yang; Yu Fang; Hongling Yuan; Wei Li; Honglin Zhu; Fangping Zhao; Jinlei Ding; Yunshu Zhu; Sizhen Wang; Guochen Sun; Hongbin Ni; Tonghui Ma; Ting Lei

doi:10.1016/j.jgg.2021.12.012

Volume 49 Issue 7

Jul. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(7): 645-653

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Characteristics of TP53 germline variants and their correlations with Li-Fraumeni syndrome or Li-Fraumeni-like syndrome in Chinese tumor patients

doi: 10.1016/j.jgg.2021.12.012

a Department of Respiratory and Critical Care Medicine, Lung Cancer Treatment Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
b Department of Translational Medicine, Genetron Health (Beijing) Technology, Co. Ltd., Beijing 102206, China;
c National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China;
d Department of Thoracic Surgery, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116023, China;
e Genetron Health (Beijing) Technology, Co. Ltd., Beijing 102206, China;
f Department of Neurosurgery, The First Medical Center of PLA General Hospital, Beijing 100853, China;
g Department of Neurosurgery, Nanjing Drum Tower Hospital (Nanjing Gulou Yi Yuan), The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China

Funds:

We thank Home for Researchers editorial team (www.home-for-researchers.com) for editing English language, grammar, punctuation, spelling, and overall style of the manuscript.

Received Date: 2021-06-22
Accepted Date: 2021-12-26
Rev Recd Date: 2021-12-17
Publish Date: 2022-01-14

Abstract

Abstract

Li-Fraumeni syndrome (LFS), a rare autosomal-dominant inheritance condition, is associated with a family cancer history as well as pathogenic/likely-pathogenic TP53 germline variants (P/LP TP53 GV). The current clinical methods for detecting LFS are limited. Here, we retrospectively investigate P/LP TP53 GV among Chinese cancer patients by next-generation sequencing and evaluate its relationship with a family cancer history. A total of 270 out of 19,226 cancer patients have TP53 GV, including 53 patients with P/LP TP53 GV. Patients with P/LP TP53 GV are mainly found in male with glioma, lung cancer or sarcoma. The median age of diagnosis for P/LP TP53 GV patients is significantly lower than that of non-P/LP TP53 GV patients (31-years vs. 53-years; P < 0.01). One LFS patient and 3 Li-Fraumeni-like syndrome (LFL) patients are among the 26 followed-up P/LP TP53 GV patients. Among 25 types of P/LP TP53 GV, the highest variant frequencies occurred at codon 175 and 248. p.M237I, p.R158H, p.C238Y and p.C275R, are firstly identified among the Chinese LFS/LFL patients. This study reports the (P/LP) TP53 GV characteristics of Chinese pan-cancer patients. These findings suggest analyzing the P/LP TP53 GV in cancer patients is an effective strategy for identifying cancer predisposition syndrome.
- Li-Fraumeni syndrome,
- TP53 germline variants,
- Pathogenic,
- Likely-pathogenic,
- Family cancer history

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