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Genetics Home Reference: your guide to understanding genetic conditions
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TP53

Reviewed January 2015

What is the official name of the TP53 gene?

The official name of this gene is “tumor protein p53.”

TP53 is the gene's official symbol. The TP53 gene is also known by other names, listed below.

What is the normal function of the TP53 gene?

The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way.

The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors.

Because p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the "guardian of the genome."

How are changes in the TP53 gene related to health conditions?

breast cancer - increased risk from variations of the TP53 gene

Inherited changes in the TP53 gene greatly increase the risk of developing breast cancer as part of a rare cancer syndrome called Li-Fraumeni syndrome (described below). These inherited mutations are thought to account for less than 1 percent of all breast cancer cases.

Non-inherited (somatic) mutations in the TP53 gene are much more common, occurring in approximately 20 to 40 percent of all breast cancer cases. These somatic mutations are acquired during a person's lifetime and are present only in tumor cells. The cancers associated with somatic mutations are typically not inherited and do not occur as part of a cancer syndrome. Many of these mutations change single protein building blocks (amino acids) in the p53 protein. These mutations lead to the production of a nonfunctional version of this protein. The defective protein builds up in cells and cannot regulate cell growth and division.

In some cases of breast cancer, one copy of the TP53 gene is lost and the remaining copy has a mutation that prevents the cell from producing any p53. Without this protein, DNA damage accumulates and cells divide in an uncontrolled way, leading to a cancerous tumor. Mutations in the TP53 gene are associated with larger tumors and more advanced disease than breast cancers without TP53 mutations. Recurring tumors are also more likely to have mutations in the TP53 gene.

bladder cancer - associated with the TP53 gene

Somatic TP53 gene mutations in bladder cells have been found in some cases of bladder cancer. Most of these mutations change single amino acids in p53. The altered protein cannot bind to DNA, preventing it from effectively regulating cell growth and division. As a result, DNA damage accumulates in cells. These abnormal cells may divide in an uncontrolled way, leading to the growth of a cancerous tumor. Mutations in the TP53 gene may help predict whether bladder cancer will progress and spread to nearby tissues, and whether the disease will recur after treatment.

head and neck squamous cell carcinoma - associated with the TP53 gene

Somatic mutations in the TP53 gene have been found in nearly half of all head and neck squamous cell carcinomas (HNSCC). This type of cancerous tumor occurs in the moist lining of the mouth, nose, and throat. Most of the TP53 gene mutations involved in HNSCC change single amino acids in p53; these changes impair the protein's function. Without functioning p53, DNA damage builds up in cells, and they can continue to divide without control, leading to tumor formation.

Li-Fraumeni syndrome - associated with the TP53 gene

Although somatic mutations in the TP53 gene are found in many types of cancer, Li-Fraumeni syndrome appears to be the only cancer syndrome associated with inherited mutations in this gene. More than 60 different mutations in the TP53 gene have been identified in individuals with Li-Fraumeni syndrome. These mutations are typically inherited from a parent and are present in all of the body's cells.

Many of the mutations associated with Li-Fraumeni syndrome change single amino acids in the part of the p53 protein that binds to DNA. Other mutations delete small amounts of DNA from the gene. Mutations in the TP53 gene lead to a version of p53 that cannot effectively regulate cell growth and division. Specifically, the altered protein is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to the growth of tumors.

other cancers - associated with the TP53 gene

Somatic mutations in the TP53 gene are the most common genetic changes found in human cancer, occurring in about half of all cancers. In addition to the cancers described above, TP53 mutations have been identified in several types of brain tumor, colorectal cancer, a type of bone cancer called osteosarcoma, a cancer of muscle tissue called rhabdomyocarcinoma, and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney).

Most TP53 mutations change single amino acids in the p53 protein, which leads to the production of an altered version of the protein that cannot bind effectively to DNA. This defective protein can build up in the nucleus of cells and prevent them from undergoing apoptosis in response to DNA damage. The damaged cells continue to grow and divide in an unregulated way, which can lead to cancerous tumors.

Where is the TP53 gene located?

Cytogenetic Location: 17p13.1

Molecular Location on chromosome 17: base pairs 7,668,401 to 7,687,549

The TP53 gene is located on the short (p) arm of chromosome 17 at position 13.1.

The TP53 gene is located on the short (p) arm of chromosome 17 at position 13.1.

More precisely, the TP53 gene is located from base pair 7,668,401 to base pair 7,687,549 on chromosome 17.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about TP53?

You and your healthcare professional may find the following resources about TP53 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the TP53 gene or gene products?

  • Antigen NY-CO-13
  • Cellular tumor antigen p53
  • P53
  • P53_HUMAN
  • P53 Tumor Suppressor
  • Phosphoprotein p53
  • Transformation-related protein 53; TRP53
  • TRP53
  • tumor protein p53 (Li-Fraumeni syndrome)
  • Tumor suppressor p53

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding TP53?

acids ; adrenal glands ; apoptosis ; cancer ; carcinoma ; cell ; cell division ; colorectal ; DNA ; DNA damage ; gene ; genome ; hormone ; inherited ; kidney ; mutation ; nucleus ; osteosarcoma ; phosphoprotein ; protein ; radiation ; syndrome ; tissue ; toxic ; transcription ; transcription factor ; transformation ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Damineni S, Rao VR, Kumar S, Ravuri RR, Kagitha S, Dunna NR, Digumarthi R, Satti V. Germline mutations of TP53 gene in breast cancer. Tumour Biol. 2014 Sep;35(9):9219-27. doi: 10.1007/s13277-014-2176-6. Epub 2014 Jun 15. (http://www.ncbi.nlm.nih.gov/pubmed/24929325?dopt=Abstract)
  • Gene Review: Li-Fraumeni Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1311)
  • Lacroix M, Toillon RA, Leclercq G. p53 and breast cancer, an update. Endocr Relat Cancer. 2006 Jun;13(2):293-325. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16728565?dopt=Abstract)
  • Lorenzo Romero JG, Salinas Sánchez AS, Giménez Bachs JM, Sánchez Sánchez F, Escribano Martínez J, Hernández Millán IR, Segura Martín M, Virseda Rodríguez JA. p53 Gene mutations in superficial bladder cancer. Urol Int. 2004;73(3):212-8. (http://www.ncbi.nlm.nih.gov/pubmed/15539839?dopt=Abstract)
  • Loyo M, Li RJ, Bettegowda C, Pickering CR, Frederick MJ, Myers JN, Agrawal N. Lessons learned from next-generation sequencing in head and neck cancer. Head Neck. 2013 Mar;35(3):454-63. doi: 10.1002/hed.23100. Epub 2012 Aug 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22907887?dopt=Abstract)
  • Masica DL, Li S, Douville C, Manola J, Ferris RL, Burtness B, Forastiere AA, Koch WM, Chung CH, Karchin R. Predicting survival in head and neck squamous cell carcinoma from TP53 mutation. Hum Genet. 2014 Aug 10. [Epub ahead of print]. (http://www.ncbi.nlm.nih.gov/pubmed/25108461?dopt=Abstract)
  • Merino D, Malkin D. p53 and hereditary cancer. Subcell Biochem. 2014;85:1-16. doi: 10.1007/978-94-017-9211-0_1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/25201186?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7157)
  • Olivier M, Langerød A, Carrieri P, Bergh J, Klaar S, Eyfjord J, Theillet C, Rodriguez C, Lidereau R, Bièche I, Varley J, Bignon Y, Uhrhammer N, Winqvist R, Jukkola-Vuorinen A, Niederacher D, Kato S, Ishioka C, Hainaut P, Børresen-Dale AL. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006 Feb 15;12(4):1157-67. (http://www.ncbi.nlm.nih.gov/pubmed/16489069?dopt=Abstract)
  • Sengupta S, Harris CC. p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol. 2005 Jan;6(1):44-55. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15688066?dopt=Abstract)
  • Silwal-Pandit L, Vollan HK, Chin SF, Rueda OM, McKinney S, Osako T, Quigley DA, Kristensen VN, Aparicio S, Børresen-Dale AL, Caldas C, Langerød A. TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance. Clin Cancer Res. 2014 Jul 1;20(13):3569-80. doi: 10.1158/1078-0432.CCR-13-2943. Epub 2014 May 6. (http://www.ncbi.nlm.nih.gov/pubmed/24803582?dopt=Abstract)
  • Varley JM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat. 2003 Mar;21(3):313-20. Review. Erratum in: Hum Mutat. 2003 May;21(5):551. (http://www.ncbi.nlm.nih.gov/pubmed/12619118?dopt=Abstract)
  • Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer. 2002 Aug;2(8):594-604. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12154352?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2015
Published: March 23, 2015