oncogene

An oncogene is a gene that has the potential to cause cancer when mutated or expressed at high levels. In normal cells, the corresponding gene is a proto-oncogene, which encodes proteins that regulate cell growth, division, and survival. Oncogenes arise through mutations that create a gain of function, as well as through gene amplification or chromosomal rearrangements that lead to overexpression or constitutive activity. Viral integration can also introduce oncogenic activity by hijacking host genes.

Oncogene activation can occur via several mechanisms, including point mutations that lock signaling proteins in an active state, gene amplification increasing the amount of a growth-promoting protein, and chromosomal translocations that generate fusion genes with continuously active products. Activation can be dominant: a single altered allele may drive uncontrolled proliferation.

Prominent examples of oncogenes include the RAS family (KRAS, NRAS, HRAS), which encode small GTPases involved in signaling; ERBB2/HER2, often amplified in breast cancer; MYC family transcription factors (c-MYC, N-MYC) that drive proliferation; BCR-ABL fusion in chronic myeloid leukemia; and receptor tyrosine kinases such as ALK or RET with activating alterations. Oncogenes can also arise from viral origins, with viral oncogenes contributing to malignant transformation.

Clinical relevance includes the use of targeted therapies that inhibit oncogene products, such as tyrosine kinase inhibitors (imatinib, erlotinib), HER2-directed therapies (trastuzumab), and KRAS G12C inhibitors (sotorasib). Oncogenes are a central concept in cancer biology, representing a class of genetic alterations that promote tumor initiation and progression while informing diagnostic and therapeutic strategies.