5th March 2024

Oncogenes

Oncogenes are highly conserved DNA segments responsible for regulating normal cell growth. They often express growth factors, growth factor receptors, nuclear transcription factors and signal transduction molecules. Oncogene activation can occur via:

• Amplification of oncogene – HER2 amplification in breast cancer
• Point mutation or intragenic deletion – EGFR mutation in lung cancer, KIT mutation in gastrointestinal stromal tumours, RET mutation in MEN2
• Chromosomal rearrangement – BCR-ABL fusion gene in CML ( t9:22 fusion gene); mantle cell lymphoma (t11:14 translocation); Burkitt lymphoma (t8:14 translocation); Acute promyelocytic leukaemia (t15:17 translocation)

Most oncogenes exert a dominant influence as only one mutated copy of the gene is sufficient to result in the malignant transformation of the cell. Most oncogene mutations are gain-of-function mutations that result in abnormal or increased gene expression and increasing protein levels.