Protoonkogene

Proto-oncogenes (protoonkogene in German) are normal genes that encode proteins regulating cell growth, division, differentiation, and survival. They play essential roles in development and tissue homeostasis. When a proto-oncogene is altered by mutations, gene amplification, or mis-regulation, it can become an oncogene—an altered gene that drives cancer progression. Oncogenes typically act dominantly, meaning that a single activating change in one allele can contribute to tumorigenesis.

Activation mechanisms include point mutations that lock a protein in an active state (as seen with RAS family members), gene amplification resulting in overexpression (as with MYC), or chromosomal rearrangements that create fusion proteins with constitutive activity (as with BCR-ABL in leukemias or various MYC translocations). Proto-oncogenes include genes encoding receptor tyrosine kinases (such as ERBB2/HER2), cytoplasmic signaling proteins (RAS), and transcription factors (MYC family). Other examples include activating mutations in BRAF and FGFRs, and amplification of MET, among others.

Clinical relevance: mapping proto-oncogenes and their activated forms informs targeted cancer therapies, such as tyrosine kinase inhibitors for EGFR or HER2, and BCR-ABL inhibitors for chronic myeloid leukemia. Cancer development is typically multifactorial, involving additional genetic and epigenetic changes.