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?
Code for proteins that regulate normal growth.
(growth factors & receptors)
How does the Rb gene -ve regulate mitosis?
Rb gene codes for pRb
E2F promotes DNA synthesis
-> pRb deactivates E2F
What other mutations can mimic pRb loss?
- Mutational activation of Cyclin D or CDK4 (their complex phosphorylates & 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
Inherited
Explain inherited oncogenesis:
- One allele of Rb gene is inherited defective
- Other copy undergoes somatic point mutation
Explain sporadic oncogenesis?
Both ‘hits’ or mutations occur in a single cell (i.e. not inherited)
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
Multiple Endocrine Neoplasia
Examples of Familial Cancers:
Some breast or ovarian cancers
How can an proto-oncogene become an oncogene?
Altered structure by mutation
Dysregulation of expresssion by gene amplification/overexpression
What do oncogenes code for?
Oncoproteins
e.g. growth factors, nuclear regulatory proteins, cell cycle regulators etc
