Normal Function
The RB1 gene provides instructions for making a protein called pRB. This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way. Under certain conditions, pRB stops other proteins from triggering DNA replication, the process by which DNA makes a copy of itself. Because DNA replication must occur before a cell can divide, tight regulation of this process controls cell division and helps prevent the growth of tumors. Additionally, pRB interacts with other proteins to influence cell survival, the self-destruction of cells (apoptosis), and the process by which cells mature to carry out special functions (differentiation).
Health Conditions Related to Genetic Changes
Retinoblastoma
Hundreds of mutations in the RB1 gene have been identified in people with retinoblastoma, a rare type of eye cancer that typically affects young children. This cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color. Researchers estimate that 40 percent of all retinoblastomas are germinal, which means that RB1 mutations occur in all of the body's cells and can be passed to the next generation. The other 60 percent are non-germinal, which means that RB1 mutations occur only in the eye and cannot be passed to the next generation.
In germinal retinoblastoma, an RB1 mutation is present in all of the body's cells. For retinoblastoma to develop, the other copy of the RB1 gene also must be mutated or lost. This second mutation typically occurs early in life in retinal cells. Cells with two altered copies of the RB1 gene produce no functional pRB and are unable to regulate cell division effectively. As a result, retinal cells lacking functional pRB can divide uncontrollably to form cancerous tumors. Some studies suggest that additional genetic changes can influence the development of retinoblastoma; these changes may help explain variations in the development and growth of tumors in different people.
In people with germinal retinoblastoma, RB1 mutations increase the risk of several other cancers outside the eye. Specifically, these people are more likely to develop a cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and an aggressive form of skin cancer called melanoma.
Non-germinal retinoblastoma occurs in people with no history of the disorder in their family. Affected individuals are born with two normal copies of the RB1 gene. Then, usually in early childhood, both copies of the gene in retinal cells acquire mutations or are lost. These non-inherited genetic changes are known as somatic mutations. Somatic mutations in both copies of the RB1 gene prevent the cells from producing any functional pRB. The loss of this protein allows retinal cells to grow and divide without control or order, leading to the development of a cancerous tumor.
More About This Health ConditionBladder cancer
Somatic RB1 gene mutations have been identified in people with bladder cancer. These changes prevent pRB from regulating cell division effectively, leading to uncontrolled growth and division of affected cells and tumor formation.
More About This Health ConditionCholangiocarcinoma
MedlinePlus Genetics provides information about Cholangiocarcinoma
More About This Health ConditionLung cancer
Somatic mutations in the RB1 gene have also been found in lung cancer. As in other forms of cancer, these genetic changes make the pRB protein ineffective, and cells can grow and divide without control, forming a tumor.
More About This Health ConditionOther cancers
Somatic mutations in the RB1 gene are associated with many other types of cancer. In addition to the cancers listed above, changes in the RB1 gene have been reported in some cases of breast cancer, melanoma, and a bone cancer known as osteosarcoma. Somatic RB1 mutations have also been identified in some leukemias, which are cancers of blood-forming cells. Somatic RB1 mutations in cancer cells inactivate pRB so it can no longer regulate cell division effectively.
Other Names for This Gene
- p105-Rb
- PP110
- PPP1R130
- RB
- RB1 gene
- RB_HUMAN
- retinoblastoma 1
- Retinoblastoma 1 (including osteosarcoma)
- Retinoblastoma-1
- Retinoblastoma-associated protein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
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- Sampieri K, Hadjistilianou T, Mari F, Speciale C, Mencarelli MA, Cetta F, Manoukian S, Peissel B, Giachino D, Pasini B, Acquaviva A, Caporossi A, Frezzotti R, Renieri A, Bruttini M. Mutational screening of the RB1 gene in Italian patients with retinoblastoma reveals 11 novel mutations. J Hum Genet. 2006;51(3):209-216. doi: 10.1007/s10038-005-0348-3. Epub 2006 Feb 4. Citation on PubMed
- Wolff EM, Liang G, Jones PA. Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer. Nat Clin Pract Urol. 2005 Oct;2(10):502-10. doi: 10.1038/ncpuro0318. Citation on PubMed
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