Mechanisms of Oncogenesis

Question 1

What is Cancer?
→ How can it spread?

What is a Tumour/Neoplasm?
→ What are the 2 types of it?

Answer 1

• Disease in which abnormal cells divide uncontrollably and can invade nearby tissues
  → Through Blood and Lymph
• Abnormal mass of tissue that results when cells divide more than they should
  → Benign (non-cancerous) or Malignant (cancerous)

Question 2

CARCINOGENESIS:
What are the 4 stages in the Multistage Theory?

How can a Single cell lead to cancer?
→ How many of these mutations are required for Carcinogenesis to occur?
→ What are Passenger mutations?

Answer 2

• 1. Initiation - Interaction of Carcinogen with DNA
     
     2. Promotion - Selective growth advantage, Early Pre-cancer (Adenoma), REVERSIBLE at this stage
     3. Progression - Enhanced cell division, Later Pre-cancer (Late Adenoma), REVERSIBLE at this stage
     4. Malignant Conversion - Now is a Cancer, NON-REVERSIBLE at this stage
• Develops oncogenic Driver mutations
  → 2-8 Driver mutations
  → Mutations that occur due to the loss of function of key DNA repair genes

Question 3

CARCINOGENS:
What are they?
——————-

Chemical:
Give an example

What are Procarcinogens? What are they converted by?

How do Tumour promotors and Tumour initiators relate?

What are Alkylating-like agents used in? Give examples
→ How do these act on DNA?
——————-

Physical:
Give examples

How does UV radiation (Non-ionising) affect DNA?
→ What does a failure to repair this lead to?
——————-

Viral:
Give 2 examples and what cancer they lead to?

How can Virus-infected cells become cancer cells?

What properties does a Virus need to be considered a Carcinogen?

Answer 3

• Substances and exposures that can lead to cancer
• e.g. Alkylating agents (Chemotherapy)
• Indirect Carcinogens (e.g. benzo(a)pyrene) - converted by Liver Microsomes
• Tumour promotors are substances that are only effective if applied after the Tumour initiators
• Platinum-based Chemotherapy drugs (Cisplatin, Carboplatin)
  → Irreversibly bind to G and crosslink the two strands to prevent separation during replication
  ——————-
• e.g. UV, X-rays
• Forms Pyrimidine (Thymine, Cytosine) Dimers - Cyclobutane Pyrimidine Dimers (CPD) and Pyrimidine-Pyrimidone (6-4 PP)
  → Mutations and Translocations
  ——————-
• e.g. Hep B can lead to Liver Cancer, HPV can lead to Cervical Carcinoma
• Expression of viral oncogenes, which can result in the integration of viral genes into the host genome
• • Stable association with cells - Chromosome integration or Episome formation
  • Doesn’t kill cells - Non-permissive host (virus can’t replicate), Suppression of lytic cycle, Viral release by budding
  • Immunoevasion - Immunosuppression, No expression of viral antigens on host surface

Question 4

Hereditary Cancer Predisposition Syndromes:
Give 2 examples

How can Gene mutations lead to cancer?

How can Chromosomal abnormalities lead to cancer?

What else can predispose one to cancer?

Answer 4

• e.g. Li-Fraumeni Syndrome, Down Syndrome
• Activate oncogenes and/or Inactive tumour suppressor genes e.g. Lynch Syndrome
• Translocations (e.g. Leukaemia) and Numerical disorders (e.g. Trisomy in Down syndrome)
• Inherited immune system problems e.g. Ataxia Telangiectasia