Abstract
BackgroundMutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups.MethodsA systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival.ResultsTP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner.ConclusionsThe mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.
Highlights
Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC)
Survival analysis of TP53 mutational landscape reveals novel prognostic signatures We aimed to investigate whether the presence of mutations in the TP53 gene correlated with the prognosis of HNSCC
Multivariate Cox regression analysis confirmed that TP53 mutation was an independent prognostic factor in HNSCC patients (Fig. 1)
Summary
Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). It is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. CONCLUSIONS: The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks. Mutations of the tumour-suppressor gene TP53 are among the most common genomic alterations occurring in malignancy, including head and neck squamous cell carcinoma (HNSCC). Several studies have shown that such carcinogens contribute to the mutational profile of TP53.6–9
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