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
Describe the oncogene transcriptional activators in terms of the proto-oncogene they arise form, they’re activation
Nuclear regulatory proteins
Myc
Translocation
Describe the oncogene cycling in terms of the proto-oncogene they arise form, they’re activation
Cell cycle regulators
Cyclin D
Translocations and amplification
Describe the oncogene CDK’s in terms of the proto-oncogene they arise form, they’re activation and the types of cancer they are involved in
Cell cycle regulators
CDK4
Amplification
What is the mechanism of viral carcinogenesis?
- virus genome inserted in the host causing proto-oncogene overexpression within the cell
- retrovirus inserts an oncogene in the host DNA
What is the mechanism of chemical carcinogenesis?
-chemical carcinogens can covalently bind to DNA forming DNA add cuts that can cause tumour suppressor gene deactivation or oncogene activation
What is the mechanism of physical carcinogenesis (radiation)
Bases are susceptible to attack by radiation eg. UV
What is the multi-step process fo tumour formation? (6)
- Carcinogen affects DNA of a normal cell
- Cause mutation in the DNA
- Can inactivate tumour suppressor genes and activate oncogenes
- dysregulation
- tumour progression
- malignant neoplasm
