Lecture 32: Genes and cancer Flashcards
What causes cancer?
Cancers are induced by mutations in cancer causing genes
- Acquired or somatic mutations in majority
- Somtimes inherited
Which genes cause cancer?
Oncogenes (cancer driver)
Tumour suppressor genes
Genes involved in regulation of apoptosis
Also now;
- Epigenetic changes
- Abnormalities of DNA repair genes
- Non-coding RNA changes i.e microRNA
What are oncogenes?
Dominant acting genes - transform cells
Normal state = Proto-oncogenes
Activated to oncogene
What does oncogenes encode?
Most encode proteins involved in signalling
- Growth factor ligands
- Growth factor receptors (inc. signalling, constituently active)
- Intracellular signal transmission
- Nuclear transcription factors
What do oncogenes do to normal cells?
Transforms normal cells to neoplastic cells
- Increased cell proliferation
- Block normal cell differentiation
What genetic factors can lead to the activation of oncogenes?
- Gene amplification
- Over expression of gene
- Point mutations
- Chromosome translocations
What is an example of oncogene amplification?
Her2 amplification in breast cancer
What is the clinical significance of Her2?
Her-2 is a proto-oncogene, it encodes for an epidermal growth factor receptor in mammary cells.
(Her2 protein overexpressed in 30% of cases, and of these 90% have Her2 amplification)
Whats the clinical significance of Her2?
Target of Herceptin (monoclonal AB)
What results in the overexpression of a gene?
Mutation in its promoter region
How do chromosome translocations activate proto-oncogenes?
Form fusion gene which encodes for novel protein with increased activity.
Increased expression of oncogene
What are tumour suppressor genes?
- Recessive acting or ‘anti-oncogenes’
- Requires loss of activity, both alleles
i.e in most cases one inherited mutation and one aquired in the other allele
What did the tumour suppressor gene hypothesis come from?
Retinoblastoma
- TSP are recessive thus inheritance has bilateral onset
- Non-inherited takes a mutation event of each allele for onset thus later onset and tends to be unilateral.
i.e two hit hypothesis
Describe the cancer genes involved in apoptosis?
- Upregulation of genes which encode for proteins that block apoptosis
- Loss of activity of genes which encode for proteins that mediate apoptosis
Does a single gene mutation cause cancer?
Most cancers involve multiple genetic events or hits before full cancer phenotype develops.
