TP53 PATHOGENIC VARIANTS RELATED TO CANCER

Abstract

TP53 or P53 is a tumor suppressor gene known as the “genome guardian”, responsible for inducing cell response to DNA damage, by stopping the cell cycle in case of mutation, activating DNA repair enzymes, initiating senescence and activation of apoptosis. Mutations in the gene sequence can cause non-synonymous mutations or errors in the reading frame by insertion, deletion or displacement of nucleotides: e.g., c.358A>G mutation in exon 4 and variants located in exons 9 and 10 of the TD domain. Therefore, in this review, we will see that changes in the reading frame, including the loss of one or two base pairs could prevent accurate transcription or changes in the structure and function of the protein, and could completely impair reparation function. These changes promote self-sufficiency in growth signaling, insensitivity to anti-growth signals, and evasion of apoptosis, resulting in limitless replication and induction of metastatic angiogenesis, generating as a consequence the proliferation of tumor, neoplastic, and lymphoid cells. Taking into account the importance of TP53 in the regulation of the cell cycle, the objective of this review is to update information related to the role of this gene in the development of cancer and the description of genetic variations.

Keywords

• neoplasms
• nuclear phosphoprotein p53
• tumor suppressor
• mutation
• clinvar
• uniprot