Having a technically strong NGS panel with simple and consistent library preparation is critical for variant detection. The Archer® VariantPlex™ p53 Kit combines superior TP53 gene coverage with robust enrichment chemistry and an easy-to-use workflow to give you confident, sensitive and quantitative TP53 variant calling.
For Research Use Only. Not for use in diagnostic procedures.
|Input DNA Required||10-200ng*|
|Time Required||6 hours|
|Hands on Time||2.5 hours|
|Sample Type||Fresh Frozen, FFPE|
|Total Target Size||1.38kb|
|On Target %||>99%†|
|Coverage Uniformity >20% of Mean||~96%|
|Recommended # Reads||100,000|
*Input recommendations for FFPE samples vary depending on Archer PreSeq™ DNA QC score. 50ng input is recommended in the absence of PreSeq screening.
†As observed using genomic DNA
Tumor protein p53 is encoded by the TP53 gene, which contains 12 coding exons and is located on the short arm of chromosome 17 at position 13.1. p53 contains transcriptional activation, DNA binding, and oligomerization domains. The protein regulates the cell cycle and maintains genomic stability through many different mechanisms of action. The protein is localized in the nucleus where it functions as a transciption factor.
When DNA damage occurs due to radiation, ultra-violet light, genotoxic drugs, nutrition deprivation, or heat/cold shock, p53 is activated via the ATM-CHK2 or ATR-CHK1 DNA repair pathways. Cell nutrition deprivation and heat/cold shock can stimulate p53 directly through hypoxia and the subsequent production of nitric oxide. Once stimulated, p53 transctiptionally activates target genes (1,2). The target genes can induce apoptosis, senescence, DNA repair, changes in metabolism, and cell cycle arrest. One p53 effector, p21, is a potent negative regulator of cell cycle progression and cell division, and its up regulation results in cell cycle arrest. Pausing the cell cycle gives the cell the opportunity to make repairs, if possible, or commit to p53-mediated cell death.
Loss of p53 function through genetic mutations or disturbances in the p53-signaling pathway is a common feature in cancers. In fact, according to the International Cancer Genome Consortium, the TP53 gene is mutated in the majority of ovarian, esophageal, lung, rectal, pancreatic, oral, colon, and brain cancers. Greater than 75% of TP53 mutations result in expression of a mutant p53 protein that has lost some level of wild-type function (3). Impaired p53 can inhibit downstream tumor suppression, resulting in uncontrolled neoplastic growth. p53 has been shown to gain oncogenic functions from genetic mutations in the TP53 gene (4). The tumor-driving functions of mutant p53 include angiogenesis, stem cell expansion, survival, proliferation, enhanced chemo-resistance, mitogenic defects, metastasis, migration, and genomic instability (5-8).
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