Mutation

Mutation — oncology-focused definition

A mutation is a permanent alteration in the DNA sequence of a gene that may change gene function or expression, contributing to cancer development and progression.

Types relevant to oncology:

• Point mutations (missense, nonsense, silent)
• Insertions or deletions (indels) → may cause frameshifts
• Splice-site mutations
• Driver vs passenger mutations
  • Driver mutations confer growth advantage
  • Passenger mutations are biologically neutral

Oncology relevance:

• Mutations can:
  • Activate oncogenes (gain-of-function; e.g., KRAS, BRAF)
  • Inactivate tumor suppressor genes (loss-of-function; e.g., TP53, BRCA1/2)
• May be somatic (tumor-acquired) or germline (hereditary cancer risk).

Clinical significance (for oncology pharmacists):

• Central to precision oncology and targeted therapy selection.
• Predict:
  • Drug sensitivity (e.g., EGFR mutations → EGFR TKIs)
  • Drug resistance (e.g., KRAS mutations → anti-EGFR resistance)
• Guide prognosis, dosing, and toxicity monitoring.

Key takeaway:

Mutations are the molecular basis of cancer, driving tumor behavior and determining therapeutic options and outcomes.