RGD Reference Report - Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma. - Rat Genome Database

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Missense mutations in the TP53 DNA-binding domain predict outcomes in patients with advanced oral cavity squamous cell carcinoma.

Authors: Lapke, Nina  Lu, Yen-Jung  Liao, Chun-Ta  Lee, Li-Yu  Lin, Chien-Yu  Wang, Hung-Ming  Ng, Shu-Hang  Chen, Shu-Jen  Yen, Tzu-Chen 
Citation: Lapke N, etal., Oncotarget. 2016 Jul 12;7(28):44194-44210. doi: 10.18632/oncotarget.9925.
RGD ID: 14995497
Pubmed: PMID:27283772   (View Abstract at PubMed)
PMCID: PMC5190089   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.9925   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
oral squamous cell carcinoma  IAGP 14995497DNA:missense mutations: :multipleRGD 
oral squamous cell carcinoma  ISOTP53 (Homo sapiens)14995497; 14995497DNA:missense mutations: :multipleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)


Additional Information