# Oncogene
An oncogene is a gene that, when mutated or expressed at abnormally high levels, helps drive a normal cell toward cancer; it arises from a normal gene, called a proto-oncogene, that is involved in cell growth and division[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncogene). A proto-oncogene that is altered such that it is duplicated excessively or functions more actively than usual is termed an oncogene, and such a gene can turn healthy cells into cancerous ones and proliferate within the body[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncogene).
| Key fact | Detail |
|---|---|
| Definition | A mutated or overactive form of a proto-oncogene, a gene involved in normal cell growth and division[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncogene) |
| Inheritance | The converting mutations usually occur during a person's lifetime and are not inherited from a parent[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncogene) |
| Activation mechanisms | Point mutations, gene amplification, and chromosomal translocations that create fusion proteins[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/) |
| Effect at the cell level | Oncogenes act dominantly as gain-of-function changes, pushing the cell to divide repeatedly or escape programmed cell death[3](https://www.genome.gov/genetics-glossary/Oncogene) • [4](https://academic.oup.com/oncolo/article/29/8/658/7710154) |
| Scale | If defined as a gain-of-function cancer gene encoding a protein, the number of such genes is probably in excess of a thousand and growing[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC3428493/) |
| Prevalence example | RAS mutations are present in almost 25% of human cancers[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/) |
| Recognition | J. Michael Bishop and Harold E. Varmus shared the 1989 Nobel Prize in Physiology or Medicine for the discovery of the cellular origin of retroviral oncogenes[6](https://www.livescience.com/16342-nobel-prize-medicine-history-list.html) |
## Proto-oncogenes and their normal roles
Proto-oncogenes are normal genes in all respects, often with important functions in controlling cell proliferation, differentiation, motility, or survival signaling[7](https://www.iarc.who.int/wp-content/uploads/2018/07/wcr-3.pdf). They encode components at many levels of growth-factor signaling: MYC is a transcription factor controlling cell proliferation and metabolism, EGFR is a receptor tyrosine kinase for growth and survival pathways, KRAS is a small GTPase that switches between active GTP-bound and inactive GDP-bound states, and [Bcl-2](https://www.edgepedia.org/bcl-2) is an anti-apoptotic protein favoring cell survival[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/). In healthy tissue these genes act like an accelerator pedal, advancing division only when the surrounding signals call for it[3](https://www.genome.gov/genetics-glossary/Oncogene).
The conversion to an oncogene is a gain of function: the altered gene pushes growth regardless of normal signals, or cannot be turned off[3](https://www.genome.gov/genetics-glossary/Oncogene) • [8](https://www.cancer.gov/about-cancer/understanding/what-is-cancer). This contrasts with tumor suppressor genes, whose cancer-causing changes are losses of function; loss-of-function mutations in tumor suppressors and gain-of-function mutations in oncogenes are canonically considered pathogenic[4](https://academic.oup.com/oncolo/article/29/8/658/7710154). Most control mechanisms in the cell involve both inhibitory (tumor suppressor) and stimulatory (proto-oncogene) components, so the same kinds of effects on cell behavior can result from mutations in either class[9](https://www.ncbi.nlm.nih.gov/books/NBK26902/).
## How proto-oncogenes become oncogenes
Activation occurs through several mechanisms[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/):
- **Point mutations** that constitutively activate the protein, as in KRAS mutation, which locks the GTPase into its signaling state[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **Gene amplification**, producing overexpression, as with HER2 amplification in breast cancer[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **Chromosomal translocations** that create fusion proteins, such as BCR-ABL in chronic myeloid leukemia, a constitutively active tyrosine kinase[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **Epigenetic alterations** can also activate proto-oncogenes[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
A nearby insertion of viral DNA or a DNA rearrangement can likewise convert a normal cellular gene into an active oncogene[10](https://www.ncbi.nlm.nih.gov/books/NBK220892/pdf/Bookshelf_NBK220892.pdf). The combined activation of oncogenes and inactivation of tumor suppressor genes drives the progression of cancer[7](https://www.iarc.who.int/wp-content/uploads/2018/07/wcr-3.pdf).
## Discovery through tumor viruses
The first oncogenic retroviruses were isolated by Ellermann and Bang in 1908 and by [Peyton Rous](https://www.edgepedia.org/peyton-rous) in 1911, creating the founding paradigm of retrovirology[11](https://www.ncbi.nlm.nih.gov/sites/books/NBK19387/). [Rous sarcoma virus](https://www.edgepedia.org/rous-sarcoma-virus) (RSV), carrying the src gene, induces visible oncogenic transformation of fibroblasts within a few days[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC3428493/).
In 1976, [J. Michael Bishop](https://www.edgepedia.org/j-michael-bishop) and Harold Varmus published the conclusion that the oncogene in the virus did not represent a true viral gene but a normal cellular gene, which the virus had acquired during replication in the host cell and thereafter carried along[12](https://www.nobelprize.org/prizes/medicine/1989/press-release/?lng=en). The term proto-oncogene is applied to c-src because this cellular gene can give rise to an oncogene, whether through capture by a virus or through mutations occurring without any viral involvement[13](https://www.ncbi.nlm.nih.gov/books/NBK190623/). This finding suggested that retroviral capture of a normal cellular gene alone would be insufficient to create an oncogene; the gene must sustain a mutation to cause cancer[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC3501656/). More than thirty cellular genes were discovered by finding in cellular DNA a gene closely related to a retroviral oncogene, and still more were found later in other ways[13](https://www.ncbi.nlm.nih.gov/books/NBK190623/). Bishop and Varmus received the 1989 [Nobel Prize in Physiology or Medicine](https://www.edgepedia.org/nobel-prize-in-physiology-or-medicine) for the discovery of the cellular origin of retroviral oncogenes[6](https://www.livescience.com/16342-nobel-prize-medicine-history-list.html).
## Major oncogenes and the cancers they drive
Several well-characterized oncogenes illustrate the range of mechanisms and cancer types[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/):
- **RAS** (KRAS, HRAS, NRAS) regulates cell growth, proliferation, differentiation, and survival through the MAPK and PI3K pathways; oncogenic RAS mutations appear in almost 25% of human cancers, including colorectal and pancreatic cancer[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **MYC** is a transcription factor that modulates thousands of genes; its amplification is particularly common in breast cancer, neuroblastoma, and certain lung cancers, and high MYC expression often correlates with poor prognosis[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **HER2 (ERBB2)** drives mammary gland development normally; HER2-positive disease accounts for 15 to 20% of breast cancers, and overexpression or amplification is associated with poor survival[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **BRAF** activates the MEK-ERK cascade; the V600E mutation accounts for about 90% of BRAF mutations in cancer and occurs in 40 to 60% of melanomas[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **BCR-ABL** results from a chromosomal translocation and is diagnostic for chronic myeloid leukemia[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
- **EGFR** overexpression or activating mutations are common in non-small cell lung cancer, glioblastoma, and head and neck squamous cell carcinoma[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/).
Other examples listed in cancer-gene surveys include RET in thyroid cancer, PDGF in glioma, and BCL2 in [B cell](https://www.edgepedia.org/b-cell) lymphoma[15](https://www.preprints.org/frontend/manuscript/043ae0dc56a8aade00139c83b35fa15b/download_pub).
## When the categories blur
The oncogene-versus-tumor-suppressor classification is a model, and some genes do not fit one side. Evidence in gliomas shows that NOTCH can function as both tumor suppressor and oncogene even within the same tissue type[4](https://academic.oup.com/oncolo/article/29/8/658/7710154). A 2003 review found mounting evidence that Notch signaling is not exclusively oncogenic and can instead function as a tumor suppressor[16](https://pubmed.ncbi.nlm.nih.gov/14570040/). The p63 gene, a relative of p53, has been the subject of a similar debate, with in vivo evidence supporting roles in both tumor suppression through apoptosis and oncogenic behavior in tumors[17](https://www.sciencedirect.com/science/article/abs/pii/S0959437X05002145). The functional distinction that matters most, as the cell-biology literature puts it, is not between the two gene classes but between genes lying in different biochemical and regulatory pathways[9](https://www.ncbi.nlm.nih.gov/books/NBK26902/).
## Therapeutic targeting
Agents that target oncogenes and their associated pathways are in clinical use, with many more in preclinical and clinical testing; the candidate-drug pool has grown through antibodies, small synthetic molecules, cytokines, and gene therapy techniques[18](https://academic.oup.com/oncolo/article/9/4/361/6387589). Clinical successes have been limited by the redundancy of many cancer-related pathways and the high variability in genotype and phenotype among individual tumors[18](https://academic.oup.com/oncolo/article/9/4/361/6387589). Current therapeutic strategies include inhibitors of KRAS and MYC and attempts to restore tumor-suppressor gene function, with drug resistance and tumor heterogeneity remaining major challenges[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/). Because cancer cells often rely heavily on their abnormal behaviors, therapies that target these features, such as drugs aimed at specific gene mutations, can be effective, and a few targeted treatments apply to any cancer carrying the targeted mutation regardless of where it started[8](https://www.cancer.gov/about-cancer/understanding/what-is-cancer).
## References
1. [Definition of oncogene, NCI Dictionary of Cancer Terms, National Cancer Institute](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oncogene)
2. [Singh, S. R. et al. (2025). Exploring the Genetic Orchestra of Cancer: The Interplay Between Oncogenes and Tumor-Suppressor Genes. Cancers 17(7):1082.](https://pmc.ncbi.nlm.nih.gov/articles/PMC11988167/)
3. [Oncogene, National Human Genome Research Institute Genetics Glossary](https://www.genome.gov/genetics-glossary/Oncogene)
4. [Understanding variants of unknown significance and classification of genomic alterations, The Oncologist](https://academic.oup.com/oncolo/article/29/8/658/7710154)
5. [Retroviral Oncogenes: A Historical Primer, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3428493/)
6. [Nobel Prize in Medicine: 1901-Present, Live Science](https://www.livescience.com/16342-nobel-prize-medicine-history-list.html)
7. [Oncogenes and Tumour Suppressor Genes, IARC/WHO](https://www.iarc.who.int/wp-content/uploads/2018/07/wcr-3.pdf)
8. [What Is Cancer?, National Cancer Institute](https://www.cancer.gov/about-cancer/understanding/what-is-cancer)
9. [The Molecular Basis of Cancer-Cell Behavior, Molecular Biology of the Cell, 4th ed., NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK26902/)
10. [Free Executive Summary, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK220892/pdf/Bookshelf_NBK220892.pdf)
11. [The Development of Retrovirology as Intellectual History, Retroviruses, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/sites/books/NBK19387/)
12. [The Nobel Prize in Physiology or Medicine 1989, Press Release, NobelPrize.org](https://www.nobelprize.org/prizes/medicine/1989/press-release/?lng=en)
13. [Retroviruses and Their Replication Cycle, The Art and Politics of Science, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK190623/)
14. [The History of Tumor Virology, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3501656/)
15. [Unraveling the Co[relation of Oncogenes and Tumor Suppressor Genes], Preprints.org](https://www.preprints.org/frontend/manuscript/043ae0dc56a8aade00139c83b35fa15b/download_pub)
16. [Radtke, F., Raj, K. (2003). The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nature Reviews Cancer 3:756-767.](https://pubmed.ncbi.nlm.nih.gov/14570040/)
17. [Mills, A. A. (2006). p63: oncogene or tumor suppressor? Current Opinion in Genetics & Development 16:38-44.](https://www.sciencedirect.com/science/article/abs/pii/S0959437X05002145)
18. [Oncogenes and Tumor Suppressor Genes in Breast Cancer: Potential Diagnostic and Therapeutic Applications, The Oncologist](https://academic.oup.com/oncolo/article/9/4/361/6387589)
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*Topic: Encyclopedia › Life and health › Biological foundations › Genetics and genomic reference › Gene structure, expression, and regulation*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license