01Normal genes with a dangerous side
A proto-oncogene is a normal gene that promotes growth — growth factors, receptors, signaling proteins, transcription factors. When it becomes hyperactive, it's called an oncogene. Because the effect is a gain of function, a mutation in just one allele can drive cancer: oncogenes act dominantly.
The first oncogene (SRC) was discovered in a chicken virus; the virus had picked up a mutated copy of a normal host gene. That insight — cancer genes are corrupted versions of our own — earned a Nobel Prize.
02Four routes to activation
Point mutation changes a protein so it's stuck on (RAS G12D). Gene amplification makes extra copies (HER2 in ~20% of breast cancers, MYCN in neuroblastoma). Chromosomal translocation creates a fusion protein or puts a gene under a strong promoter — the Philadelphia chromosome fuses BCR to ABL; in Burkitt lymphoma, MYC moves next to antibody-gene enhancers.
Finally, insertional activation: a virus integrates next to a proto-oncogene and drives its expression.