## Oncogenes: Definition and Mechanism **Key Point:** Oncogenes are mutated or overexpressed versions of normal proto-oncogenes that drive cellular transformation. They act in a DOMINANT manner — only one mutated copy is needed to confer a growth advantage. ### Dominant vs. Recessive Inheritance Pattern Oncogenes exhibit **dominant inheritance** at the cellular level: - A single mutated allele is sufficient to promote transformation - The mutant protein product actively drives proliferation or blocks apoptosis - This contrasts with tumor suppressors (e.g., p53, Rb), which are recessive — both copies must be lost ### Mechanisms of Oncogene Activation | Mechanism | Example | Outcome | | --- | --- | --- | | Point mutation | RAS (codon 12, 13, 61) | Constitutive GTPase activity | | Gene amplification | MYC, HER2 | Excessive protein production | | Chromosomal translocation | BCR-ABL (Philadelphia chromosome) | Abnormal fusion protein | | Insertional mutagenesis | Retroviral insertion | Promoter activation | **High-Yield:** The defining feature of oncogenes is their **dominant action** — one "hit" is enough. This is why a single BCR-ABL fusion in chronic myeloid leukemia drives disease. ### Proto-oncogenes Proto-oncogenes are normal cellular genes encoding: - Growth factors (PDGF) - Growth factor receptors (EGFR, HER2) - Signal transducers (RAS, RAF) - Transcription factors (MYC, JUN) When mutated or dysregulated, they become oncogenes. **Clinical Pearl:** In familial cancer syndromes with germline oncogene mutations (rare), affected individuals inherit one mutated copy and require only a single somatic hit in target tissues — this explains the dominant inheritance pattern seen in families. [cite:Robbins 10e Ch 7]
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