Cancer as Clonal Evolution: Drivers, Passengers and Selection in a Tissue · seed 1 · A4, ink-friendly. The answer key prints on its own page for grown-ups.

A tumour as evolution inside one tissue

Science · Genetics & Evolution · ages 22-23
Name ______________________   Date ____________

  1. What best argues that a gene is a plausible driver?

    • High frequency within a single tumour alone
    • Recurrence across independent tumours at the same functional sites
    • A long gene name that sounds important

  2. What is a driver mutation in a tumour population?

    • A neutral change carried along by a dividing clone
    • A sequencing error introduced by the machine
    • A beneficial change that expands its carrier clone under selection

  3. A mutation found in every tumour cell came earlier than one found in a small fraction.

    Circle one:   True   False

  4. Two mutations nest: mutation A is in all cells, mutation B only inside the A clone. What is the order?

    • B came first, then A spread around it
    • A and B must have struck at the same instant
    • A was the founding lesion and B struck later within that branch

  5. A gene is mutated once at a random spot in one patient. How do you judge it?

    • A certain driver because it was observed
    • More likely a passenger until recurrence says otherwise
    • Proof that selection never acts in tumours

  6. How do drift and hitchhiking apply to a growing tumour?

    • Neutral passengers hitchhike beside the sweeping driver clone
    • Every mutation in a tumour is selected for growth
    • Clones never expand because tissues block all division

  7. A colleague calls a gene a driver from one high frequency tumour alone. What is missing?

    • Nothing; single tumour frequency proves selection
    • A larger tumour sequenced with a different machine
    • Recurrence across patients plus a selection argument for the allele

  8. Resistance explodes weeks after therapy starts. What does clonal structure suggest?

    • Therapy created the resistant clone from nothing at high speed
    • A rare resistant subclone pre-existed and therapy selected it
    • Passengers turned into drivers because the drug watched them
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Answer key

For grown-ups. Fold this page away before handing over the rest.

A tumour as evolution inside one tissue W1-mt_3qIJZwD0m5-s1

  1. Recurrence across independent tumours at the same functional sites · Repeated hits across patients stand out against the noisy background.
  2. A beneficial change that expands its carrier clone under selection · Drivers speed growth, so selection sweeps their clones to high frequency.
  3. True · Shared mutations predate the last expansion, while fraction-only ones came later.
  4. A was the founding lesion and B struck later within that branch · Nested frequencies reconstruct the order from founding lesion to later subclone.
  5. More likely a passenger until recurrence says otherwise · Frequency within one tumour means little, while recurrence across tumours means a lot.
  6. Neutral passengers hitchhike beside the sweeping driver clone · A driver sweeps, and neutral alleles beside it ride along to high frequency.
  7. Recurrence across patients plus a selection argument for the allele · One tumour cannot separate a swept driver from a hitchhiking passenger.
  8. A rare resistant subclone pre-existed and therapy selected it · Fresh selection expands what was already there, so relapse outruns fresh mutation.
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