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TP53 gene
tumor protein p53

Normal Function
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 (proliferating) 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."

Health Conditions Related to Genetic Changes

Breast cancer
Inherited changes in the TP53 gene greatly increase the risk of developing breast
cancer, as well as several other forms of cancer, as part of a rare cancer syndrome
called Li-Fraumeni syndrome (described below). These mutations are thought to
account for only a small fraction of all breast cancer cases.
Noninherited (somatic) mutations in the TP53 gene are much more common than
inherited mutations, occurring in 20 to 40 percent of all breast cancers. These
somatic mutations are acquired during a person's lifetime and are present only in
cells that become cancerous. The cancers associated with somatic mutations do not
occur as part of a cancer syndrome. Most of these mutations change single protein
building blocks (amino acids) in the p53 protein, which reduces or eliminates the
protein's tumor suppressor function. This altered p53 protein cannot regulate cell
proliferation effectively. Specifically, it 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 tumor growth.
Compared with breast cancers without TP53 gene mutations, tumors with these
genetic changes tend to have a poorer prognosis. They are more likely to be
 aggressive, to be resistant to treatment with certain anti-cancer drugs and radiation,
and to come back (recur) after treatment.

Bladder cancer
Somatic TP53 gene mutations have been found in some cases of bladder cancer.
Most of these mutations change single amino acids in p53. This altered p53 protein
cannot regulate cell proliferation and it 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 tumor growth.
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.

Cholangiocarcinoma

Head and neck squamous cell carcinoma

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, cell proliferation is not regulated. As a
result, cells accumulate DNA damage and continue to divide in an uncontrolled way,
leading to tumor growth.

Li-Fraumeni syndrome
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. This condition greatly increases the risk of
developing several types of cancer, including breast cancer; bone cancer; and
cancers of soft tissues (such as muscle) called soft tissue sarcomas, particularly in
children and young adults. At least 140 different mutations in the TP53 gene have
been identified in individuals with Li-Fraumeni syndrome.
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. These mutations result in an altered p53 protein that
cannot regulate cell proliferation effectively and 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.

Lung cancer
Somatic mutations in the TP53 gene have been found in nearly half of all lung
cancer. Lung cancer is a disease in which certain cells in the lungs become abnormal

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 and multiply uncontrollably to form a tumor. Signs and symptoms may not occur in
early stages of the disease.
Lung cancer is generally divided into two types, small cell lung cancer and non-
small cell lung cancer, based on the size of the affected cells when viewed under
a microscope. Small cell lung cancers nearly always have TP53 gene mutations;
however, these mutations may also occur in non-small cell lung cancer. TP53 gene
mutations change single amino acids in p53, which impair the protein's function.
Without functioning p53, cell proliferation is not regulated effectively and DNA
damage can accumulate in cells. Such cells may continue to divide in an uncontrolled
way, leading to tumor growth. Additional genetic, environmental, and lifestyle factors
contribute to a person's cancer risk; in lung cancer, the greatest risk factor is being a
long-term tobacco smoker.

Melanoma

Ovarian cancer
Somatic TP53 gene mutations are common in ovarian cancer, occurring in almost
half of ovarian tumors. These mutations result in a p53 protein that is less able to
control cell proliferation. Specifically, it 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 tumor growth.

Wilms tumor

Other cancers
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, somatic TP53 gene mutations have been identified in several
types of brain tumor, colorectal cancer, liver cancer, a type of bone cancer called
osteosarcoma, a cancer of muscle tissue called rhabdomyosarcoma, 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 control cell proliferation
and 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 tumor growth.

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Chromosomal Location
Cytogenetic Location: 17p13.1, which is the short (p) arm of chromosome 17 at position
13.1
Molecular Location: base pairs 7,668,402 to 7,687,550 on chromosome 17 (Homo
sapiens Updated Annotation Release 109.20190905, GRCh38.p13) (NCBI)

Credit: Genome Decoration Page/NCBI

Other Names for This Gene

• antigen NY-CO-13
• cellular tumor antigen p53
• P53
• P53 tumor suppressor
• P53_HUMAN
• phosphoprotein p53
• transformation-related protein 53
• TRP53
• tumor protein p53 (Li-Fraumeni syndrome)
• tumor suppressor p53

Additional Information & Resources

Educational Resources
• Molecular Biology of the Cell (fourth edition, 2002): Cell-Cycle Progression is
Blocked by DNA Damage and p53: DNA Damage Checkpoints
https://www.ncbi.nlm.nih.gov/books/NBK26856/#A3240
• Molecular Cell Biology (fourth edition, 2000): Mutations in p53 Abolish G1
Checkpoint Control
https://www.ncbi.nlm.nih.gov/books/NBK21551/#A7158

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• National Cancer Institute: Genetics of Breast and Gynecologic Cancers (PDQ)
https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq
• The TP53 Website: p53 Mutations in Lung Cancer
http://p53.free.fr/Database/p53_cancer/p53_Lung.html

Clinical Information from GeneReviews

• Li-Fraumeni Syndrome
https://www.ncbi.nlm.nih.gov/books/NBK1311

Scientific Articles on PubMed

• PubMed
https://www.ncbi.nlm.nih.gov/pubmed?term=%28%28TP53%5BTI%5D%29+OR+
%28p53%5BTI%5D%29%29+AND+english%5Bla%5D+AND+human%5Bmh%5D
+AND+%22last+180+days%22%5Bdp%5D

Catalog of Genes and Diseases from OMIM

• TUMOR PROTEIN p53
http://omim.org/entry/191170

Research Resources
• Atlas of Genetics and Cytogenetics in Oncology and Haematology
http://atlasgeneticsoncology.org/Genes/P53ID88.html
• Cancer Genetics Web: TP53
http://www.cancerindex.org/geneweb/TP53.htm
• ClinVar
https://www.ncbi.nlm.nih.gov/clinvar?term=TP53%5Bgene%5D
• HGNC Gene Symbol Report
https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11998
• Monarch Initiative
https://monarchinitiative.org/gene/NCBIGene:7157
• NCBI Gene
https://www.ncbi.nlm.nih.gov/gene/7157
• UniProt
https://www.uniprot.org/uniprot/P04637

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Sources for This Summary
• Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung
adenocarcinoma. Nature. 2014 Jul 31;511(7511):543-50. doi: 10.1038/nature13385. Epub 2014 Jul
9. Erratum in: Nature. 2014 Oct 9;514(7521):262. Rogers, K [corrected to Rodgers, K].
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25079552
Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231481/
• 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.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24929325
• 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.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22907887
Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715072/
• Masciari S, Dillon DA, Rath M, Robson M, Weitzel JN, Balmana J, Gruber SB, Ford JM, Euhus D,
Lebensohn A, Telli M, Pochebit SM, Lypas G, Garber JE. Breast cancer phenotype in women with
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2012 Jun;133(3):1125-30. doi: 10.1007/s10549-012-1993-9. Epub 2012 Mar 4.
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Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709568/
• 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. 2015 May;134(5):497-507. doi: 10.1007/s00439-014-1470-0. Epub 2014 Aug 10.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25108461
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10.1007/978-94-017-9211-0_1. Review.
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• National Cancer Institute: Genetics of Breast and Gynecologic Cancers (PDQ)
https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq
• Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences,
and clinical use. Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001008. doi: 10.1101/
cshperspect.a001008. Review.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20182602
Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827900/
• 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.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16489069
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Aalfs CM, Wagner A, Ausems MG, Hoogerbrugge N, van Asperen CJ, Gomez Garcia EB, Meijers-
Heijboer H, Ten Kate LP, Menko FH, van 't Veer LJ. TP53 germline mutation testing in 180 families
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different familial phenotypes. J Med Genet. 2010 Jun;47(6):421-8. doi: 10.1136/jmg.2009.073429.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20522432

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 • Schneider K, Zelley K, Nichols KE, Garber J. Li-Fraumeni Syndrome. 1999 Jan 19 [updated 2013
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Reprinted from Genetics Home Reference:

https://ghr.nlm.nih.gov/gene/TP53

Reviewed: December 2017

Published: November 26, 2019

Lister Hill National Center for Biomedical Communications

U.S. National Library of Medicine
National Institutes of Health
Department of Health & Human Services

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