Oncogenes And Tumour Suppressor Genes Flashcards
Function of a proto-oncogene?
Control differentiation and proliferation to regulate homeostasis
What are Ras - tumour suppressor or oncogenes?
Oncogenes
How are Ras genes activated and what do they cause?
Ras are G-proteins which are activated by the GPCR tyrosine kinase
Activation of Ras activates the MAPK(kinase) pathway causing cell proliferation and growth
What happens if there is a mutation to the Ras protein?
Switched on all the time causing constant proliferation. Doesn’t need the tyrosine kinase receptor to activate it.
Why are Ras mutations easy to detect?
Only nine bases can be changed
What kind of cancers are Ras mutations common in?
Epithelial cancers such as
- colon
- bladder
- lung
Where can mutations be found for Ras?
Codons 12, 13 and 61
How can the type of Ras mutation be an indicator of prognosis in colorectal cancer?
Eg there are two mutations which are highly significantly associated with a high risk of recurrence and a lower two year survival rate than other mutations
What is insertional mutagenesis?
When a DNA virus incorporates a viral oncogene into the host DNA.
What can cause insertional mutagenesis?
HPV 16 and 18 - cervical cancer
Hep B - hepatocellular cancer
What is a chromosomal translocation?
When a fragment of one chromosome attaches to another non-homologous chromosome
Give some examples of chromosome translocations that can lead to cancer
9;22 - chronic myeloid leukaemia leading to abnormal tyrosine kinase activity (Philadelphia chromosome)
8;14 - burkitt’s lymphoma leading to constitutive MYC expression
What is an example of gene amplification and in which cancer is it seen?
Human epidermal growth factor receptor 2 (HER-2).
Amplified and over-expressed in 20-30% of breast cancers
Linked to poor prognosis
What can gene amplification be detected by?
FISH
Immunohistochemistry
What can breast cancer with HER-2 amplification be treated with?
Herceptin - a monoclonal antibody which binds to the receptor and prevents growth by preventing downstream signalling.
Also flags HER2+ cells for destruction by the immune system