//When the guardian loses function

When the guardian loses function

The tumor-suppressor protein p53 is encoded by the TP53 gene on human chromosome 17. The protein p53 has been nicknamed “The Guardian of the Genome” because of the essential role this transcription factor plays in cell division and prevention of tumor formation. Its main function lies in its response to diverse cellular stresses for regulation of gene expression for cell cycle arrest, apoptosis, senescence, changes in metabolism, and DNA repair. First mapped in the mid 1980s and subsequently designated “Molecule of the Year” in 1993 for its role in cancer, this protein has been studied extensively for its role in transcriptional regulation and tumor progression1.

The protein p53 is highly relevant in cancer research as nearly 50% of all known human cancers contain somatic mutations in the TP53 gene. Mutations that have been identified and studied with relevance to tumors include single nucleotide variations (SNV), insertion-deletions (indels), duplications, deletions, missense mutations, non-sense mutations, and frameshift mutations in various regions of the gene such as the untranslated region (UTR) and exons2. Mutations often suppress the cancer-combating function of the gene, giving the cancer cells a survival advantage. Academic researchers and pharmaceutical companies around the world have tested numerous drugs and novel therapies that can affect the oncogenic mutations of TP53 for treating patients3. Since the 1980s, studying of the p53 protein and characterization of TP53 mutations have continued to play a significant role in our understanding of tumor progression.

Today in the field of precision medicine, identifying somatic and germline variants accurately in this gene can help determine the cause of certain diseases and cancers, predict the likely outcome of the disease, and inform the appropriate treatment for a wide range of cancer types. Targeted sequencing using an NGS panel designed to target the TP53 gene is performed to detect TP53 mutations. The NGS assays is typically conducted using DNA purified from the peripheral blood, bone marrow aspirate, and tissue sections.

The CleanPlex® TP53 Panel is expertly designed by scientists at Paragon Genomics to produce high quality data with excellent coverage uniformity (>95%). This 29-amplicon panel spans all exons of TP53 (2,080 bp) to target oncogenically relevant SNVs and indels. The CleanPlex TP53 Panel simplifies the analysis of TP53 mutations, utilizing a fast and streamlined workflow that can be completed in just 3 hours with no more than 75 minutes of hands-on time. The panel is powered by Paragon Genomics’ highly sensitive CleanPlex technology and can be used with DNA input amounts as low as 10 ng of genomic DNA or 20 ng of DNA from  formalin-fixed paraffin embedded (FFPE) samples.

 

References:

  1. National Library of Medicine – OMIM database entry on TP53
  2. ClinVar data for TP53
  3. Targeting Therapies for the p53 Protein in Cancer Treatments. Levine A.J. Annu. Rev. Cancer Biol. (2019) 3:1.1–1.14
2019-07-29T13:59:44+00:00 July 26th, 2019|Blog|Comments Off on When the guardian loses function