Tumour pathology 5 Flashcards
What do tumour-supressor genes normally do?
- Negatively regulate mitosis (Rb gene)
- Regulate Apoptosis (p53)
- Regulate DNA repair (p53)
What do proto-oncogenes do?
Normal genes that Codes for normal growth resulting proteins (growth factors and receptors)
How does the Rb gene negatively regulate mitosis?
Rb gene codes for pRb
Activates and Loses its affinity for E2F transcription factor (which promotes DNA synthesis)
What other mutations can mimic pRb loss?
- Mutational activation of Cyclin D or CDK4 (their complex phosphorylates and deactivates pRb)
- Mutational inactivation of CDK inhibitors
What does Cyclin D/CDK4 complex normally do?
Phosphorylates pRb causin it to deactivate.
Allows E2F to promote cell division
[Occurs when external stimuli signal for mitosis to occur]
Another name for Tumour-Supressor genes?
Anti-Oncogenes
whats the two-hit hypothesis:?
Two mutations are required to inactivate tumour-suppresor genes
What are the two forms of oncogenesis? (mutation to anti-oncogenes)
Sporadic (over time)
Inherited (early age)
Explain inherited oncogenesis:
- One allele of Rb gene is inherited defective
- The Other copy undergoes somatic point mutation
Explain sporadic oncogenesis?
Both ‘hits’ or mutations occur in a single cell
Whats the difference between an inherited cancer syndrome and a familial cancer?
Inherited Cancer syndrome:
- Strong family histroy of unusual cancers
- Autosomal Dominant inheritance of a single mutant gene
Familial Cancer:
- Family cluster of cancers
- Multifactorial inheritance
- Individual predisposition is unclear
Examples of inherited cancer syndromes?
- Familial Retinoblastoma
- FAP
Examples of Familial Cancers:
Some breast or ovarian cancers
How can an proto-oncogene become an oncogene?
- Mutation causes altered structure
- Dysregulation of expresssion by gene
- overexpression
What do oncogenes code for?
Oncoproteins
e.g. growth factors, nuclear regulatory proteins, cell cycle regulators
