Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma.
TP53 mutations have been linked to reduced survival in patients with oral cavity squamous cell carcinoma (OSCC). However, the impact of different types of TP53 mutations remains unclear. Here, we demonstrate that the carriage of missense mutations in the TP53 DNA binding domain (DBD missense mutations) is associated with decreased disease-specific survival (DSS) compared with wild-type TP53 (P=0.002) in a cohort of 345 OSCC patients. In contrast, DSS of patients bearing all of the remaining TP53 mutations did not differ from that observed in wild-type TP53 patients (P=0.955). Our classification method for TP53 mutations was superior to previously reported approaches (disruptive, truncating, Evolutionary Action score, mutations in L2/L3/LSH) for distinguishing between low- and high-risk patients. When analyzed in combination with traditional clinicopathological factors, TP53 DBD missense mutations were an independent prognostic factor for shorter DSS (P=0.014) alongside with advanced AJCC T- and N-classifications and the presence of extracapsular spread. A scoring system that included the four independent prognostic factors allowed a reliable patient stratification into distinct risk groups (high-risk patients, 16.2%). Our results demonstrate the usefulness of TP53 DBD missense mutations combined with clinicopathological factors for improving the prognostic stratification of OSCC patients.
ACT Genomics, Taipei, Taiwan, ROC.
Nina
N
Lapke
ACT Genomics, Taipei, Taiwan, ROC.
Yen-Jung
YJ
Lu
Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Chun-Ta
CT
Liao
Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Li-Yu
LY
Lee
Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Chien-Yu
CY
Lin
Department of Medical Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Hung-Ming
HM
Wang
Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Shu-Hang
SH
Ng
ACT Genomics, Taipei, Taiwan, ROC.
Shu-Jen
SJ
Chen
Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
Tzu-Chen
TC
Yen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D004247:DNA
TP53 DNA-binding domain; biomarker; missense mutations; oral cavity squamous cell carcinoma; outcome