Carla - Oncogenesis Question

Question 1

List three tumour suppressor genes

Answer 1

P53

Retinoblastoma associated protein

P21

Question 2

Write a note on p53
(3)

Answer 2

• It binds to regulatory sites in the genome
• Here it begins production of proteins that halt cell division until the damage is repaired
• Or if damage is too severe, p53 initiates apoptosis and permanently removes the damage

Question 3

Write a note on p53 oncogenesis
(3)

Answer 3

o Between 50 and 60% of cancers result from p53 mutations
o 90% of the time it is a missense mutation -> this causing a change in amino acid which affects the functioning of the protein
o Mutated p53 gains oncogenic functions

Question 4

What cancers are caused by a p53 mutation?

Answer 4

Li-fraumeni syndrome -> inherit only one working copy of p53 -> leads to development of many cancers:
-stomach
-pancreatic
-colon
-skin
-lung

Question 5

Write a note on retinoblastoma associated protein

Answer 5

• First tumour suppressor discovered
• Responsible for a major G1 checkpoint
• Responsible for blocking S-phase entry and cell growth
• Central regulator of the cell cycle

Question 6

Write a note on cancers caused by mutations in retinoblastoma associated protein

Answer 6

o hereditary retinoblastoma often caused by germline/inherited mutations in RB 1 gene

Question 7

Write a note on p21

Answer 7

• Also called Cyclin-dependent kinase inhibitor 1 or CDKn1a
• Expressed by p53 when DNA damage is detected
• Inhibits the CDKs needed for cell cycle progression -> puts cell into arrest
• Also inhibits the cyclins found in S and G1 phase

Question 8

Write about the oncogenesis processes of p21
(3)

Answer 8

o Cell cycle continues even if p53 has detected DNA damage -> p21 doesn’t put cell into arrest
o Low levels of p53 mean low levels of p21 -> DNA damage not detected or fixed
o In oncogenesis it can prevent apoptosis if overexpressed (leads to tumours)

Question 9

What cancers are brough about by mutations in p21
(4)

Answer 9

o Overexpressed in oesophageal
o Overexpressed in soft tissue sarcomas
o Overexpression in gliomas
o Also seen in ovarian cancer

Question 10

Write a note on proto-oncogenes
(5)

Answer 10

• Genes whose products promote cell growth and division
• Positive cell cycle regulators
• Encode:
  o Transcription factors that stimulate expression of other genes
  o Signal transduction molecules that stimulate cell division
  o Cell-cycle regulators that move through the cell cycle

Question 11

What are oncogenes?

Answer 11

• Proto-oncogenes that have gained an amplification or activating mutation that results in them gaining the ability to transform a cell into a cancer cell

Question 12

List examples of oncogenes

Answer 12

Ras
Myc
CDK4
BCR/ABL
BCL-2

Question 13

Write a note on Ras
(4)

Answer 13

 KRAS, HRAS, NRAS
 Normal = important role in cell signalling
 Mutation = point mutation -> conversion of glycine to valine -> protein doesn’t function efficiently
 Oncogenesis = drives tumour growth in many types of cancer e.g. colorectal

Question 14

Write a note on Myc
(4)

Answer 14

 C-Myc, n-Myc
 Normal = family of regulators and proto-oncogenes that codes for transcription factors. Responsible for proliferation, differentiation, apoptosis and metabolism
 Mutation = c-Myc translocation from chr 8 to chr 12
 Oncogenesis = Development of Burkitt Lymphoma

Question 15

Write a note on CDK4

Answer 15

 Normal = phosphorylates the tumour suppressant retinoblastoma gene
 Mutations = Point mutation
 Oncogenesis = Melanoma -> causes tumours

Question 16

Write a note on BCR/ABL
(2)

Answer 16

 Chimeric gene caused by a fusion of genes BCR and ABL via chromosomal rearrangement in the ‘Philadelphia Chromosome’
 Oncogenesis = this causes chronic myelogenous leukaemias

Question 17

Write a note on BCL-2

Answer 17

 Normal = regulation of apoptosis -> blocks apoptosis
 Oncogenesis = overexpression -> prevents apoptosis -> seen in lymphomas