Wk 10: Oncogenes

Question 1

What is a silent mutation?

Answer 1

• No change in aa sequence
• In non-coding DNA regions that don’t affect gene function

Question 2

What are germline mutations?

Answer 2

• Hereditary mutations
• Found in germ cells (eggs + sperm)

Question 3

What are somatic mutations?

Answer 3

Occur in non reproductive cells - can’t be passed down

Question 4

Gain of function mutations require what?

Answer 4

One gene mutated (most common)

Question 5

Loss of function mutations require what?

Answer 5

Both genes mutated (rare)

Question 6

In loss of function, why is one mutation still tolerated?

Answer 6

Second gene compensates for loss

Question 7

What are proto-oncogenes?

Answer 7

Code for proteins that drive normal cell growth

Question 8

What happens when there is deregulation of proto-oncogenes?

Answer 8

Gives rise to oncogenes = cause cancer

Question 9

What are the types of mechanisms by which proto-oncogenes become oncogenes?

Answer 9

• Point mutation
• Translocation
• Gene amplification

Question 10

Give examples of common oncogenes + the types of cancer it results in

Answer 10

• EGFR: Bladder, breast
• ERBB2: Breast, ovarian, stomach
• MYC: small cell lung cancer, colon

Question 11

What are mitogens?

Answer 11

Stimulatory signals that stimulate proliferation

Question 12

In the absence of mitogens, what happens to cells?

Answer 12

Enter G0 phase

Question 13

Give examples of mitogens + their functions

Answer 13

• PDGF: connective tissue
• EGF: mesodermal
• FGF: fibroblast
• IL: T lymphocyte
• EPO: RBC

Question 14

Which mitogen causes an inhibition in proliferation?

Answer 14

TGF-β

Question 15

Outline the MAPK signalling pathway

Answer 15

Mitogen activated protein kinases:

• RTK receptor dimerises
• Relays phosphorylation
• RAS→RAF→MEK→ERK
• Nuclear translocation of phosphorylated ERK
• Inc proliferation

Question 16

What happens when ERK enters the nucleus?

Answer 16

• Cell growth + survival
• Angiogenesis
• Migration/invasion

Question 17

Epidermal growth factors (EGF) stimulate growth in which type of cells?

Answer 17

Epidermal + epithelial cells

Question 18

Give examples of EGFR functioning as an oncogene + activating MAPK signalling

Answer 18

• Overexpression of EGFR = inc signalling
• Mutation at kinase domain = always active
• Deletion of ligand binding domain = Always active

Question 19

Mutations of EGFR overexpression are associated with what?

Answer 19

• Adenocarcinoma of lung
• Rectal cancer
• Glioblastoma
• Epithelial tumour of head + neck

Question 20

Give examples of drugs given to inhibit EGFR receptors

Answer 20

Cetuximab

Question 21

Give examples of drugs that inhibit EGFR dimerisation

Answer 21

• Trastuzumab
• Pertuzumab

Question 22

Give examples of drugs that inhibit tyrosine kinase

Answer 22

• Gefitinib
• Erlotinib
• Lapatinib

Question 23

What happens when mutations occur downs stream the MAPK signalling?

Answer 23

Cell proliferation even in absence of EGF hormone

Question 24

What does a mutation in BRAF produce?

Answer 24

Drug sensitive tumour