TP53 is the gene on chromosome 17 that encodes the p53 tumor suppressor protein. Mutations in TP53 are present in 96% of high-grade serous ovarian cancer. Many types of mutations in p53 have been characterized. These include single base substitutions leading to missense or nonsense mutations and single base deletions or insertions leading to frameshift mutations or in-frame deletions or insertions. 80% of these mutations occur in the DNA binding domain, encoded by amino acid residues 102 to 292, leading to a loss of the ability to bind DNA and act as a transcription factor. Given the rate at which TP53 is mutated in HGSOC, it comes at no surprise that it is a hot target for therapy. However, the wide range of TP53 mutations found in HGSOC present a major difficulty in TP53 targeted therapy because treatment must be specific for the mutation present.
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