Tumour Pathology 5 Flashcards
What does the retinoblastoma gene mutation cause?
Cell proliferation
What other two mutations in genes can cause the losing of retinoblastoma?
Mutational activation of the CDK4/Cyclin D complex
Mutational deactivation of the CDK’s
What inhibits the Cyclin D/CDK4 activated complex?
INK4A/P16 or P21
Describe the inherited form of the mutated retinoblastoma gene
- one defective form inherited
- somatic point mutation of other copy of retinoblastoma
Describe the sporadic form
-both mutations occur in single cell
What are the four aeitological agents of cancer (cancergenesis)
Heredity - passing on defective genes
Inherited cancer syndrome - strong family history of uncommon site-specific cancer and autosomal dominant inheritance of single mutant gene eg. Inherited Rb
Familial cancers - family clustering of cancer but individual predisposition unclear and multi-factorial inheritance
Autosomal recessive syndromes of defective DNA repair
What are the known somatic and inherited mutations of anti -oncogenes:
APC - signal transduction Rb - cell cycle regulation P53 - cell cycle arrest at G1/ apoptosis/ DNA repair P16(INK4A) - inhibits CDK’s BRCA 1/2 - DNA repair
What are proto-oncogenes?
Normal genes that code for proteins controlling cell cycle
What do proto-oncogenes mutate to form?
Oncogenes
What are examples of proto-oncogens
Growth factors
Growth factor receptors
Proteins involved in signal transduction
What causes the activation of oncogenes?
- alteration of proto-oncogene structure (through point mutations, chromosomal rearrangement and translocation)
- dysregulation of the proto-oncogene expression (gene amplification/ over-expression)
What oncoprotein products do oncogenes generate?
- growth factors
- growth factor receptors
- signal transduction proteins
- nuclear regulator protein
- cell cycle regulators
Describe the oncogene PDGF in terms of the oncoprotein, proto-oncogene they arise form, they’re activation
Oncoprotein - growth factor
Porto-oncogene - sis
Activation - overexpression
Describe the oncogene EGF-receptor family in terms of the proto-oncogene they arise form, they’re activation
Growth factor receptor
Erb-B2
Amplification
Describe the oncogene GTP- binding in terms of the proto-oncogene they arise form, they’re activation
Signal transducer
Ras
Point mutation
