Cancer

Question 1

Cancer

Answer 1

• Group of diseases characterised by uncontrolled cell division and spread of abnormal cells
• Dysregulation of checkpoints of cell division/cells escape cell cycle control mechanism
• Tumour → genetically identical cells derived from a single mutant cell

Question 2

Effects of gene mutation

Answer 2

• Cell continues to divide when proto-oncogenes → oncogenes → tell cell to grow and divide more rapidly
• Cell fails to stop uncontrolled cell growth → mutations in tumour suppressor genes
• Cells make mistakes when repairing DNA errors → mutation in DNA repair gene

Question 3

Causative factors of cancer (4)

Answer 3

1. Environmental factors
2. Loss of immunity due to infection with certain viruses
3. Genetic predisposition
4. Age

Question 4

1. Environmental factors

Answer 4

• Exposure to carcinogens (eg. tar in cigarette smoke, asbestos etc.)
• Ionising radiation (e.g. uv radiation, X-rays)
• Cause mutations that lead to cancer

Question 5

2. Loss of immunity due to infection with certain viruses

Answer 5

• HIV can weaken immune system and reduces body’s ability to fight infections by other viruses that can cause to cancer
• E.g., Karposi’s sarcoma-associated Herpes virus genome can integrate into part of the human genome that controls DNA synthesis, or that affects cell division or that affects tumour suppression pathways and may lead to cancer

Question 6

3. Genetic predisposition

Answer 6

Due to gene mutations (in the germ cells) which we inherit from our parents (e.g. BRCA1 gene, a tumour suppressor gene)

Question 7

4. Age

Answer 7

Chances of getting cancer increases with age due to accumulation of mutations in a cell over a lifetime

Question 8

Proto-oncogene

Answer 8

• Normal cellular genes which codes for proteins
• Stimulate normal cell growth and division
• E.g. growth factors, growth factors receptors, transcription factors

Question 9

Mutations of proto-oncogenes (2)

Answer 9

• Proto-oncogenes → oncogenes (gain-in-function mutation (dominant))

1. Increase in amount of gene products
2. Increase in intrinsic activity

Question 10

1. Increase in amount of proto-oncogene’s gene products

Answer 10

a) Point mutation in base sequences of regulatory elements (e.g. stronger promoter created)
- ↑ frequency of transcription,

b) Gene amplification, where the number of copies of a proto-oncogene in a cell ↑ due to mistake during DNA replication
c) Chromosomal translocation such that the proto-oncogene ends up under the control of a enhancer

a-c:

• Excess production of the proto-oncogene protein product (e.g. growth factor)
• Uncontrolled cell division

d) Retroviral integration
i) Inactivate silencer
ii) Insertion of viral enhancer that upregulates
iii) Insert viral homologue of proto-oncogene

Question 11

2. Increase in intrinsic activity

Answer 11

• Point mutation within proto-oncogene
• Changes amino acid sequence of proto-oncogene protein (e.g. growth factor)
• Becomes hyperactive or more resistant to degradation
• uncontrolled cell division

Question 12

Ras gene

Answer 12

Mutation in the ras gene results in a constitutively active Ras protein that irreversibly binds to GTP and increases cell division even in the absence of growth factors

Question 13

Tumour suppressor genes

Answer 13

• Codes for protein products that inhibit cell division and prevent uncontrolled cell division
• By activating cell cycle arrest, DNA repair and/or apoptosis

Question 14

Mutations of tumour suppressor genes

Answer 14

• Loss-of-function mutation (recessive)
• Mutations in promoter or coding sequence
• Inactivation of protein products
• Both copies of the allele need to be mutated for effects to be observed

Question 15

p53 gene

Answer 15

• Codes for, p53 protein, a STF (an activator) that can activate genes involved in:
  1. Cell cycle arrest: gives cell enough time to repair damaged DNA and prevent formation of mutant daughter cells
  2. DNA repair: prevents mutations that may lead to the formation of oncogenes or inactivated tumour suppressor genes
  3. Initiating apoptosis (programmed cell death) when DNA damage is beyond repair: remove cells with damaged DNA with the potential to cause cancer

Question 16

Mutation in p53 gene

Answer 16

• Defective p53 protein
• Will not restrict cell growth and proliferation
• Cell cycle continues without repairing DNA/does not undergo apoptosis
• Mutations accumulate over time → ↑ risk of developing cancer cells
• Mutations similar to proto-oncogenes

Question 17

Benign tumour

Answer 17

• Mutations in several genes involved in regulation of cell growth, division and death
• Big mass of cells that keeps dividing, growing and not dying
• Localised and does not spread
• Non-cancerous

Question 18

Malignant tumour

Answer 18

• Benign tumour can transform into cancerous one
• More mutations accumulate
• Invasiveness (erodes normal surrounding tissue)
• Metastasis (spread to other parts)
• Primary → secondary tumours

Question 19

Why is development of cancer a multi-step process? (Part 1 - 4)

Answer 19

1. The development of cancer requires the accumulation of mutations in the genes which control regulatory checkpoints of the cell cycle in a single cell
2. This will disrupt the normal cell cycle, thus causing the cell to undergo excessive cell proliferation
3. A gain-in-function mutation is a dominant mutation where mutation in just one allele of a proto-oncogene will result in its overexpression which will result in the production of excessive amounts of growth factors or hyperactive/degradation resistant growth factors leading to excessive cell proliferation
4. Loss-of-function mutation is a recessive mutation where mutations in both alleles of a tumour suppressor gene will result in the non-functional/missing protein which will disrupt their ability to inhibit cell cycle, enable DNA repair and promote apoptosis

Question 20

Why is development of cancer a multi-step process? (Part 2 - 5)

Answer 20

5. Activation of the genes coding for telomerase result in telomeres being lengthened allowing the cell to dividing indefinitely as the chromosomes are prevented from shortening with each DNA replication cycle. (A single cell that is immortal and continues to divide will accumulate more and more mutations)
6. Loss of contact inhibition will enable the cells to grow into a benign tumour (mass of cells).
7. Angiogenesis occur within the tumour so that the blood vessels formed can transport oxygen and nutrients for its growth.
8. The presence of blood vessels can result in the formation of a malignant tumour capable of metastasising to other parts of the body via the bloodstream to form secondary tumours
9. As it takes years to accumulate these mutations, the chances of developing cancer increases with age.

Question 21

Normal cells vs Cancerous cells (8)

Answer 21

1. Nuclei (Low/high nuclei-cytoplasmic ratio)
2. Genes (Proto-oncogenes/oncogenes, not mutated/mutated tumour suppressor genes)
3. Cell division (Controlled/uncontrolled)
4. Apoptosis (Undergoes/does not undergo)
5. Contact inhibition (Yes/no)
6. Differentiation (Yes/no)
7. Cell adhesion/metastasis (Yes/no, no/yes)
8. Angiogenesis (No/yes)