Cancer 4 Flashcards
What are the 3 classes of genes implicated in cancer?
(3 marks)
- Proto-oncogene
- Tumour suppressor genes
- Caretaker genes
What do proto-oncogenes do?
(4 marks)
- Promote cell proliferation and cell survival
- Can turn oncogenic
- Gain of function mutation - enhanced normal growth, converts proto-oncogenes to oncogenes
- Only need one copy of gene to have dominant effect and drive cell towards cancer
What happens in cancer when you get a mutation in the coding sequence?
(1 mark)
Protein produced is hyperactive/ permanently active
e.g. Ras is mutated in this way in 70% of human tumours
What happens in gene amplification in cancer?
(2 marks)
- Gene is still normal but too much of normal gene is produced
- e.g. breast cancer get extreme enahancement of Her2 gene which promotes cell proliferation
What happens in chromosome rearrangement in cancer?
(2 marks)
- Rearrangement in chromosome causes a strong promoter nect to a gene that shouldn’t be overexpressed e.g. BCL2 gene overexpressed = antiapoptotic
- Or translocation between 2 chromosomes - fusion gene or protein produced (hyperactive fusion protein) e.g. leukaeimia
What does a mutation in growth inhibitory proteins cause in cancer?
Loss of function - growth is unregulated
In a recessive mutation of growth inhibitory proteins what happens?
(2 marks)
- Loose 2 copies of TS gene before pathological effect is seen e.g. p10, p53 or the retinoblastmoprotein
- This allows cells to grow with damaged DNA and can inhibit more processes
What are the different genetic events that can cause a loss of function of tumour suppressor genes?
(5 marks)
- Loss of whole chromosome
- Regional deletion (containing normal gene)
- Chromosome rearrangement
- Mutation in coding sequence: protein non-functional p10 used to regulate Akt signalling
- p10 dephosphorylates PIP3 which causes PIP2 to shut down Akt signalling
-
Epigenetic changes causing gene silencing
- remodelling complex e.g. SWI/SNF
What are inherited tumour suppresor genes - give an example.
(2 marks)
- Offspring can inherit mutation of one allele of tumour suppresor - has predisposition for tumours e.g. hereditary retinoblastoma: inherited mutation in one allel for RB TS gene (essential for regulating key part of cell cycle)
What is familial adenomatous polyposis (FAP) and Adenomatous polypsis coli (APC)?
(3 marks)
- Loss of tumour suppressor gene (both)
- APC: loss leads to polyps in in epithelial lining of colon
- Patients w/ polyps are monitored and polyps removed regularly
What is a caretaker gene mutation?
(1 mark)
- Cell mutated which leads to an accelerated conversion of normal cell to neoplastic cell
- Loss of function mutation
What do caretaker genes do?
(5 marks)
- DNA repair or prevention of DNA damage
- Different DNA mechanisms for different damages:
- DNA mismatch repair
- Nucleotide excision repair
- Double stranded DNA breaks
What is the name of the inhertied gene that makes you 80-90% more likely to develop breast cancer?
(1 mark)
Braca gene
What intermediate is NOT formed in radiolysis?
(1 mark)
Water
Why may foods act as a cancer causative factor?
(2 marks)
May carry Benzo[a]pyrene - most frequently associated carcinogens with lung cancer
Cooked/ smoked meats
What are cyclin dependent kinases?
(1 mark)
Serine threonine kinases
At what stage in the cell cycle do cyclins appear?
(4 marks)
- Some only in G phase (G1 cyclins)
- Some in late G1 and early S phase (G1/s cyclins)
- Some in S phase (S phase cyclins)
- Some in M phase (M phase cyclins)
What is the main role for CDK activity?
(1 mark)
- Regulating cell cycle events and can be enhanced or inhibited by phsophorylation
How does the cell cycle allow for DNA repair?
(2 marks)
- G2 checkpoint blocks entry into M phase thats incured DNA damage in previous phases or not properly completed S phase
- Allows for DNA repair
How can you regulate CDK?
(4 marks)
- Association with cyclins
- Association with CDK inhbitors
- Addition of phosphate groups that regulate the activity of CDK
- Addition of phosphate groups that inhibit CDK activity
Give a few examples of CDK inhibitors?
(4 marks)
p15, p16, p21 and p27
What are some of the controls put in place to control the cell cycle?
(3 marks)
- Regulated by feedback by processes in that phase
- Checkpoint in mitosis in M phase - checks chromosomes are properly attached to the spindle
- G1 checkpoint - controls transition from G1 phase to S phase
What does tumour suppressor protein RB do?
(3 marks)
- Acts as a molecular link for G1 to S transition
- Prevents cell from going to S phase bound to TF, E2F so no transition past the start
- Inactivation RB promotes chromosomal instability, angiogenesis and increased expression of E2F
What is CDK 4 inhibited by?
(1 mark)
p16
