Oncogenes and Tumour Suppressor Genes Flashcards
(52 cards)
What are the 6 hallmarks of cancer
- Disregard of signals to stop proliferating
- Disregard of signals to differentiate
- Capacity for sustained proliferation
- Evasion of apoptosis
- Ability to invade
- Ability to promote angiogenesis
What does a cell cycle checkpoint do and why
Arrest growth to ensure genetic fidelity by allowing the cell to check that everything is okay
What can permanent activation of a cyclin do
Drive a cell through a cell cycle checkpoint
What is the role of a proto-oncogene (7)
Code for essential proteins involved in the maintenance of cell growth, division and differentiation such as:
- Growth factors
- Growth factor receptors
- Intracellular transducers (signaling proteins)
- Intracellular receptors
- Transcription factors
- Cell cycle regulatory proteins
- Cell death regulators
What is the difference between a proto-oncogene and an oncogene
A single mutation which means the protein product no longer responds to control influences, can be single base mutation
Give 4 examples of proto-oncogenes that can be converted to oncogenes
SRC, MYC, Ki-RAS, Ha-RAS
What 4 mechanisms can convert a proto-oncogene to oncogenes
Mutation in the coding sequence, gene amplification, chromosomal translocation, insertional mutagenesis
What is gene amplification and what does it cause
Overproduction of normal protein because of multiple gene copies
What does a mutation in the coding sequence cause, what are examples of mutations in the coding sequence
Point mutations or deletions, causes an aberrantly active protein
What is a chromosomal translocation and what does it do? Give an example of a disease it causes
Chimaeric genes, its a strong enhancer that increases normal protein levels
What is an insertional mutagenesis? How can you get one? Example
A fusion to actively transcribed genes that overproduces proteins or a fusion protein that is hyperactive, can get one through viral infection, e.g. Philadelphia chromosome
How many copies of a proto-oncogene need to be damaged to give oncogenic properties
1
SRC: function, mechanism of activation, location, associated cancers?
Tyrosine kinase, over expression/C terminal deletion, cytoplasmic, breast/colon/lung
MYC: function, mechanism of activation, location, associated cancers?
Transcription factor, translocation, nuclear, Burkitt’s lymphoma
JUN: function, mechanism of activation, location, associated cancers?
Transcription factor, over expression/deletion, nuclear, lung
Ha-RAS: function, mechanism of activation, location, associated cancers?
G-protein, point mutation, cytoplasmic, bladder
Ki-RAS: function, mechanism of activation, location, associated cancers?
G-protein, point mutation, cytoplasmic, colon/lung
How does RAS become activated and deactivated
Binds GTP to make RAS active, then dephosphorylation to GDP makes it inactive
What cell activity are RAS proteins central to
MAPK cascade (mitogen activated protein kinase)
Which tumour are RAS oncogenes common in and rare in
Rare in breast cancer and found in 95% of pancreatic cancers
Which codon mutations inhibit GTP hydrolysis
12 (Gly), 59 (Ala) and 61 (Gln)
What is different about proto-oncogenes and tumour suppressor genes? What is the exception
Mutations are required in both copies of TSG to promote oncogenic activity rather than the one, p53 gene is the exception
What features are there of inherited cancers (6)
- Family history of related cancers
- Unusually early age of onset
- Bilateral tumours in paired organs
- Synchronous or successive tumours
- Tumours in different organ systems in same individual
- Mutations inherited through the germline
What mutation incurs retinoblastoma (gene, type of gene, chromosome)
RB1 TSG mutation on 13q14
