lect 5 - Cancaer as a Genetic Disease

🧬 Cancer as a Genetic Disease

Fun Bullet-Point Summary

🎗 Cancer is common
- ~1 in 3 people in Ireland will develop cancer
- Risk increases strongly with age
- Incidence rising, mortality slowly declining (better detection & treatment)
🧠 Cancer = a genetic disease of cells
- Caused by mutations in DNA
- Results in uncontrolled cell growth and division
🧩 Cancer is a multistep process
- Mutations accumulate over time
- Cells evade apoptosis
- Tumours stimulate angiogenesis
- Cells invade tissues and metastasize
🧬 Cancer-causing mutations
- Germline (inherited) → present in every cell
- Somatic (acquired) → arise during life
- ~90% of cancer genes show somatic mutations
- ~20% have germline mutations predisposing to cancer
👨‍👩‍👧 Features of hereditary cancer
- Early age of onset
- Multiple tumours
- Rare tumour types
- Strong family history
- Congenital abnormalities
🎯 Knudson’s Two-Hit Hypothesis
- Cancer requires multiple mutations
- Tumour suppressor genes require TWO hits
- Explains early onset in inherited cancers
⚠ Most cancer-associated SNVs are low penetrance
- Many common variants → small individual risk
- Rare variants → high penetrance
🚗 Two main gene types drive cancer
- Oncogenes = accelerator stuck on
- Tumour suppressors = brakes fail
🔥 Oncogenes
- Mutated proto-oncogenes
- Gain-of-function
- Dominant at cellular level
- Promote proliferation & survival
🛑 Tumour suppressor genes
- Loss-of-function
- Recessive at cellular level
- Both alleles must be inactivated (LoH)
🧬 Loss of heterozygosity (LoH)
- Second functional TS allele lost
- Cell becomes cancer-prone
🧠 Key cancer genes
- Oncogenes: SRC, MYC, HER2, HRAS
- Tumour suppressors: RB1, p53, BRCA1/2, MLH1, MSH2
🧪 Hallmarks of cancer
- Uncontrolled division
- Evading apoptosis
- Angiogenesis
- Immune evasion
- Telomere maintenance
- Metastasis
- Altered metabolism
🎯 Modern cancer treatment
- Genetic screening for risk
- Targeted therapies (Glivec, Herceptin)
- Gene editing
- mRNA cancer vaccines (in development)

🃏 40 Flashcards (Q → A)

What is cancer? → Uncontrolled cell growth due to genetic mutations
Lifetime cancer risk in Ireland? → ~1 in 3
Does cancer risk increase with age? → Yes
Cancer is a disease of what? → DNA
Is cancer multistep? → Yes
What is angiogenesis? → Formation of new blood vessels
What is metastasis? → Spread to distant tissues
Germline mutations are: → Inherited
Somatic mutations are: → Acquired during life
What is COSMIC? → Catalogue of cancer genes
% of cancer genes with somatic mutations? → ~90%
Hereditary cancers often occur at what age? → Younger
Knudson’s hypothesis requires how many hits? → At least two
Which cancer inspired Knudson’s work? → Retinoblastoma
What is penetrance? → Probability genotype causes phenotype
Most cancer SNVs are: → Low penetrance
Two gene classes involved in cancer? → Oncogenes & tumour suppressors
Proto-oncogenes normally do what? → Promote cell growth
Oncogene mutations are typically: → Gain-of-function
Oncogene mutations act as: → Dominant
Tumour suppressors normally do what? → Inhibit cancer
TS mutations are typically: → Loss-of-function
How many TS alleles must be lost? → Two
Loss of heterozygosity means: → Loss of remaining normal TS allele
First tumour suppressor identified? → RB1
Function of p53? → Cell cycle arrest & apoptosis
BRCA1/2 are involved in: → DNA repair
Which gene repairs double-strand breaks? → BRCA1
What is MYC? → Transcription factor
What does HER2 encode? → Growth factor receptor
HER2 amplification occurs in: → Breast cancer
Philadelphia chromosome causes: → CML
Fusion protein in CML? → BCR-ABL (p210)
Glivec targets what? → Tyrosine kinase
Why is Glivec targeted? → Only affects cancer cells
Herceptin targets: → HER2 receptor
Herceptin is what type of drug? → Monoclonal antibody
Cancer cells maintain telomeres by: → Overriding normal shortening
Cancer metabolism favors: → Aerobic glycolysis
Future cancer therapies include: → Gene editing & mRNA vaccines

📝 40 MCQs

1. Cancer is best described as:
A. An infectious disease
B. A metabolic disorder
C. A genetic disease
D. An autoimmune disease

2. Cancer is multistep because:
A. One mutation is sufficient
B. Multiple mutations accumulate
C. It always spreads
D. It always involves infection

3. Which process supplies tumours with blood?
A. Apoptosis
B. Angiogenesis
C. Metastasis
D. Differentiation

4. Germline mutations are:
A. Only in tumours
B. Acquired after birth
C. Inherited
D. Not passed on

5. Most cancer mutations are:
A. Germline
B. Somatic
C. Mitochondrial
D. Epigenetic only

6. Knudson studied:
A. Lung cancer
B. Retinoblastoma
C. Breast cancer
D. Leukaemia

7. Tumour suppressor genes require:
A. One mutation
B. Two mutations
C. Three mutations
D. Amplification

8. Oncogenes arise from:
A. Tumour suppressors
B. Repair genes
C. Proto-oncogenes
D. Telomeres

9. Oncogene mutations are usually:
A. Recessive
B. Dominant
C. Silent
D. Lethal

10. Tumour suppressor mutations are:
A. Gain-of-function
B. Dominant
C. Loss-of-function
D. Activating

11. Loss of heterozygosity refers to:
A. Gene duplication
B. Loss of normal TS allele
C. Gain of oncogene
D. Translocation

12. Which gene controls apoptosis?
A. SRC
B. MYC
C. p53
D. HER2

13. BRCA1 mutations affect:
A. Angiogenesis
B. DNA repair
C. Cell metabolism
D. Telomere length

14. HER2 amplification leads to:
A. Reduced division
B. Increased proliferation
C. Apoptosis
D. DNA repair

15. Philadelphia chromosome causes:
A. ALL
B. CML
C. Breast cancer
D. Melanoma

16. Glivec targets:
A. HER2
B. p53
C. Tyrosine kinase
D. DNA polymerase

17. Targeted therapies are effective because they:
A. Kill all dividing cells
B. Only target cancer-specific proteins
C. Damage DNA
D. Block angiogenesis only

18. Cancer hallmarks include:
A. Reduced metabolism
B. Apoptosis
C. Immune evasion
D. Differentiation

19. Telomeres in cancer cells:
A. Shorten rapidly
B. Are maintained
C. Are deleted
D. Stop replication

20. Aerobic glycolysis refers to:
A. Using oxygen efficiently
B. Fast energy production without oxygen
C. DNA synthesis
D. Cell death

21–40 continue below

21. SRC is a: A. Receptor B. Kinase C. Repair enzyme D. TS
22. MYC is a: A. Receptor B. Transcription factor C. Enzyme D. Antibody
23. HRAS mutations cause: A. Inactive signalling B. Constant signalling C. DNA breaks D. Repair failure
24. RB1 controls: A. Angiogenesis B. Cell cycle C. Metabolism D. Apoptosis
25. TS genes usually act as: A. Accelerators B. Brakes C. Switches D. Signals
26. Hereditary cancers often show: A. Late onset B. Early onset C. No family history D. Low penetrance
27. p53 is called: A. Cancer gene B. Guardian of genome C. Oncogene D. Receptor
28. Herceptin is ineffective when: A. HER2 is amplified B. HER2 is constitutively active C. Breast cancer D. Early cancer
29. Gene editing aims to: A. Kill all cells B. Restore gene function C. Create mutations D. Increase SNVs
30. mRNA cancer vaccines aim to: A. Repair DNA B. Activate immune response C. Block metabolism D. Prevent mutation
31. COSMIC catalogues: A. Germline genes B. Cancer genes C. Repair genes D. Immune genes
32. Penetrance refers to: A. Mutation rate B. Disease severity C. Probability of phenotype D. Inheritance pattern
33. Low penetrance variants are usually: A. Rare B. Common C. Lethal D. Dominant
34. Angiogenesis benefits tumours by: A. Killing cells B. Feeding tumours C. Repairing DNA D. Triggering immunity
35. Metastasis means: A. Growth B. Mutation C. Spread D. Repair
36. Apoptosis is: A. Cell growth B. Cell death C. Cell repair D. Cell division
37. Cancer cells avoid: A. Metabolism B. Angiogenesis C. Apoptosis D. Replication
38. Natural selection in tumours leads to: A. Stable genomes B. Clone expansion C. Repair D. Normal cells
39. Most cancers are caused by: A. One mutation B. Multiple mutations C. Infection D. Mitochondria
40. Precision oncology relies on: A. Random therapy B. Genetics C. Chemotherapy only D. Surgery only

lect 5 - Cancaer as a Genetic Disease

🧬 Cancer as a Genetic Disease

🃏 40 Flashcards (Q → A)

📝 40 MCQs

✅ MCQ Answer Key