Tumour Pathology 5 Flashcards
(21 cards)
How do tumour suppressor genes function?
Discourage cell growth
Temporarily halt cell division to carry out DNA repair
What is an anti-oncogene?
Tumour suppressor gene
Responsible for:
Apoptosis
DNA repair
Negative regulation of mitosis
What do mutations in retinoblastoma gene cause?
Favour cell proliferation - anti-oncogene (tumour suppressor gene)
What is the inherited form of oncogenesis?
One defective copy of RB gene
Somatic point mutation of other copy
What is the sporadic form of oncogenesis?
(no previous history or genetic defect)
Both hits occur in a single cell
What portion of cancers are hereditary?
5-10% of all cancers
Give two examples of inherited cancer syndromes?
Familial retinoblastomas
Familial adenomatous polyposis of colon
What gene is responsible for signal transduction and also FAP colon cancer?
APC
What gene is responsible for cell cycle regulation and causes retinoblastoma and osteosarcomas?
Rb
Which gene is responsible for DNA repair and causes breast and ovarian cancer?
BRCA 1/2
How does HER2 contribute to breast cancer
Tyrosine kinase receptors
Inactive growth factor receptor, receptors come together when GF binds
Mutation causes over expression of HER2
Receptor can bind more GF
How does BRAF contribute to melanoma
BRAF signal transducer
Proto-oncogene
Mutation creates BRAF V600
BRAF V600 always active, pushes cell cycle forward
(sunlight)
How can retinoblastoma gene contribute to malignancy of the eye
Hereditary mutation cause one gene to stop producing protein
Another mutation can cause remaining protein to loose function
E2F released, progression of cell cycle, no regulation
How can a mismatch pair contribute to colon cancer
MLH1 and other genes recognise and replace damaged DNA
MLH1 mutation reduces amount of p53, decrease mismatch repair, mismatch remains
DNA replication accumulates mutations
How does p53 have a role in numerous cancers
Mutation - loss of p53 function
No longer stops cell cycle at checkpoints if there is damage
How can smocking cause cancer
Numerous chemicals in cigarette smoke
Metabolised to carcinogens in liver
Released into circulation
Damages DNA
Numerous mutations eg mutations in p53
How can Human papilloma virus cause cancer
Infection of cervix
Produces E6 protein which binds and inactivates p53
Increased risk of subsequent uncontrolled cell division, precancer then cancer
How can Alcohol cause cancer
Large amounts converted to acetylaldehyde
Goes in systemic circulation
Cause double stranded breakdown of DNA in many genes
Increase cancer risk
Give examples of oncoprotein products
Growth factors
Growth factor receptors
Proteins involved in signal transduction
Nuclear regulatory proteins
Cell cycle regulators
What is c-myc
Increase proteins that drive cell cycle
Increase proteins that stop cell death
Proto-oncogene
How can c-myc promote cancer
Translocation - c-myc gene breaks off chromosome, attaches to different one
In B cell can bind beside immunoglobulin regulatory sequence
Huge increase in c-myc
