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 me...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.M237 I,p.R158 H,p.C238 Y and p.C275 R,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.展开更多
文摘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.M237 I,p.R158 H,p.C238 Y and p.C275 R,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.
