- A All cells in a tumour are sometimes thought to be genetically identical, despite the sequential acquisition of distinct driver mutations actually producing genetically divergent clonal subpopulations in most textbook accounts
- B Sequential acquisition of driver mutations produces successive clones with growth advantages; different clonal populations within one tumour leads to treatment resistance when resistant subclones survive and expand
- C Cancer is sometimes thought not to evolve over time, when tumours are in fact well understood to undergo continuous somatic evolution, with successive mutant clones gaining selective growth advantages during normal conditions
- D Tumour heterogeneity is sometimes thought to make diagnosis easier, when in clinical practice intratumour heterogeneity instead substantially complicates diagnosis and underlies treatment resistance as generally observed
Correct answer: B. Sequential acquisition of driver mutations produces successive clones with growth advantages; different clonal populations within one tumour leads to treatment resistance when resistant subclones survive and expand
Explanation: Clonal evolution (Nowell, 1976): cancer begins as a single cell with initiating mutation; subsequent mutations confer growth advantages, selected by tumour microenvironment. Intratumour heterogeneity: different regions have different driver mutations. Implications: (1) Biopsy may miss relevant mutations; (2) Drug resistance - pre-existing resistant subclones selected by treatment; (3) Liquid biopsy (circulating tumour DNA) captures heterogeneity; (4) Combination therapy needed to target multiple clones.
Concept context
Pathogens, infectious diseases, non-infectious diseases, drugs, cancer, and public health. High NEET importance.