Wk 10: Oncogenes Flashcards
What is a silent mutation?
- No change in aa sequence
- In non-coding DNA regions that don’t affect gene function
What are germline mutations?
- Hereditary mutations
- Found in germ cells (eggs + sperm)
What are somatic mutations?
Occur in non reproductive cells - can’t be passed down
Gain of function mutations require what?
One gene mutated (most common)
Loss of function mutations require what?
Both genes mutated (rare)
In loss of function, why is one mutation still tolerated?
Second gene compensates for loss
What are proto-oncogenes?
Code for proteins that drive normal cell growth
What happens when there is deregulation of proto-oncogenes?
Gives rise to oncogenes = cause cancer
What are the types of mechanisms by which proto-oncogenes become oncogenes?
- Point mutation
- Translocation
- Gene amplification
Give examples of common oncogenes + the types of cancer it results in
- EGFR: Bladder, breast
- ERBB2: Breast, ovarian, stomach
- MYC: small cell lung cancer, colon
What are mitogens?
Stimulatory signals that stimulate proliferation
In the absence of mitogens, what happens to cells?
Enter G0 phase
Give examples of mitogens + their functions
- PDGF: connective tissue
- EGF: mesodermal
- FGF: fibroblast
- IL: T lymphocyte
- EPO: RBC
Which mitogen causes an inhibition in proliferation?
TGF-β
Outline the MAPK signalling pathway
Mitogen activated protein kinases:
- RTK receptor dimerises
- Relays phosphorylation
- RAS→RAF→MEK→ERK
- Nuclear translocation of phosphorylated ERK
- Inc proliferation
What happens when ERK enters the nucleus?
- Cell growth + survival
- Angiogenesis
- Migration/invasion
Epidermal growth factors (EGF) stimulate growth in which type of cells?
Epidermal + epithelial cells
Give examples of EGFR functioning as an oncogene + activating MAPK signalling
- Overexpression of EGFR = inc signalling
- Mutation at kinase domain = always active
- Deletion of ligand binding domain = Always active
Mutations of EGFR overexpression are associated with what?
- Adenocarcinoma of lung
- Rectal cancer
- Glioblastoma
- Epithelial tumour of head + neck
Give examples of drugs given to inhibit EGFR receptors
Cetuximab
Give examples of drugs that inhibit EGFR dimerisation
- Trastuzumab
- Pertuzumab
Give examples of drugs that inhibit tyrosine kinase
- Gefitinib
- Erlotinib
- Lapatinib
What happens when mutations occur downs stream the MAPK signalling?
Cell proliferation even in absence of EGF hormone
What does a mutation in BRAF produce?
Drug sensitive tumour
