TP53
Primary Author(s)*
Beth Pitel, MS, ASCP(CG)CM
Kay Weng Choy (MBBS, BMedSci, FAACB)
Synonyms
Tumor protein p53, LFS1, p53, BCC7, TRP53
Genomic Location
Cytoband: 17p13.1
Genomic Coordinates:
chr17:7,571,720-7,590,868 [hg19]
chr17:7,668,402-7,687,538 [hg38]
Cancer Category/Type
Nearly universal involvement in diverse cancer types.
Gene Overview
Common Alteration Types
The TP53 gene contains homozygous mutations in about 50-60% of human cancers. About 90% of the mutations in TP53 encode missense mutant proteins that span about 190 codons in the DNA-binding domain; none of the 50 most common pathogenic missense mutations occur outside of the DNA-binding region. These mutations produce a protein with a reduced capacity to bind to a specific DNA sequence that regulates p53 transcriptional pathway [15]. The eight most common mutations across all cancer types (R175H, R248Q, R273H, R248W, R273C, R282W, G245S, R249S) are found in codons that account for about 28% of the total p53 mutations (See Table 1 in [15]); these alleles appear to be selected for preferentially in human cancers of many tissue types. Seven of the eight mutations occur at methylated CpG sites in TP53, which encode arginine residues that contact the DNA and are conserved over evolutionary time scales [15].
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| X | X | X | X |
Internal Pages
External Links
TP53 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
TP53 by COSMIC - sequence information, expression, catalogue of mutations
TP53 by CIViC - general knowledge and evidence-based variant specific information
TP53 by IARC - TP53 database with reference sequences and mutational landscape
TP53 by St. Jude ProteinPaint mutational landscape and matched expression data.
TP53 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
TP53 by Cancer Index - gene, pathway, publication information matched to cancer type
TP53 by OncoKB - mutational landscape, mutation effect, variant classification
TP53 by My Cancer Genome - brief gene overview
TP53 by UniProt - protein and molecular structure and function
TP53 by Pfam - gene and protein structure and function information
TP53 by GeneCards - general gene information and summaries
GeneReviews - information on Li Fraumeni Syndrome
References
1. Finlay CA, et al., (1989). The p53 proto-oncogene can act as a suppressor of transformation. Cell 57(7):1083-1093, PMID 2525423.
2. Li FP, et al., (1998). A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358-5362, PMID 3409256.
3. Malkin D, et al., (1990). Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250(4985):1233-1238, PMID 1978757.
4. Baker SJ, et al., (1990). Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249(4971):912-915, PMID 2144057.
5. Kastenhuber ER, Lowe SW, (2017). Putting p53 in context. Cell 170(6):1062-1078, PMID 28886379.
6. Kastan MB, et al., (1991). Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51(23 Pt 1):6304-6311, PMID 1933891.
7. Harper JW, et al., (1993). The p21 CDK-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75(4):805-816, PMID 8242751.
8. Serrano M, et al., (1997). Onocogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593-602, PMID 9054499.
9. Liu Y, et al., (2016). Deletions linked to TP53 loss drive cancer through p53-independent mechanisms. Nature 531(7595):471-475, PMID 26982726.
10. Ciriello G, et al., (2013). Emerging landscape of oncogenic signatures across human cancers. Nat Genet 45(10):1127-1233, PMID 24071851.
11. Shlien A, et al., (2008). Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci U S A 105(32):11264-11269, PMID 18685109.
12. Olivier M, et al., (2009). Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 16(1):1-12, PMID 18802452.
13. Malkin D, (2011). Li-Fraumeni syndrome. Genes Cancer 2(4):475-484, PMID 21779515.
14. Tinat J, et al., (2009). 2009 version of the Chompret criteria for Li-Fraumeni syndrome. J Clin Oncol 27(26):e108-109, PMID 19652052.
15. Baugh EH, et al., (2018). Why are there hotspot mutations in the TP53 gene in human cancers? Cell Death Differ 25(1):154-160, PMID 29099487.
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.