Tumour Pathology 5 COPY Flashcards
How do tumour suppressor genes function?
Discourage cell growth or temporarily halt cell division to carry out DNA repair
What is an anti-oncogene?
A tumour suppressor geneResponsible for ApoptosisDNA repair and the negative regulation of mitosis
What do mutations in retinoblastoma gene cause?
Favour cell proliferation since it is an anti-oncogene (a tumour suppressor gene)
What other mutations can cause the same effect of a mutated RB gene?
Mutational activation of Cyclin or CDK (naturally responsible for the phosphorylation of the pRB)Mutational inactivation of CDKI’s
What is the inherited form of oncogenesis?
One defective copy of the RB gene Somatic point mutation of the other copy
What is the sporadic form of oncogenesis?
Both hits occur in a single cell
What portion of cancers are hereditary?
5-10% of all cancers
Give two examples of inherited cancer syndromes?
Familial retinoblastomasFamilial adenomatous polyposis of colon
What gene is responsible for signal transduction and also FAP colon cancer?
APC
What gene is responsible for cell cycle regulation and causes retinoblastoma and osteosarcomas?
Rb
What gene inhibits CDK’s and causes malignant melanoma?
p16 (INK4a)
Which gene is responsible for DNA repair and causes breast and ovarian cancer?
BRCA 1/2
What can cause alteration of proto-oncogene structure?
Point mutationChromosome rearrangements and translocations
What can cause dysregulation of proto-oncogene expression?
Gene amplificationOverexpression
Give examples of oncoprotein products
Growth factorsGrowth factor receptorsProteins involved in signal transductionNuclear regulatory proteinsCell cycle regulators
What mutation of the PDGF growth factor causes Astrocytoma and osteosarcoma’s?
Over expression
What mutation of the growth factor receptor EGF causes Breast ovarian lung and stomach cancer?
Amplification
What mutation in GTP binding signal transducaers causes lung, colon, pancreas, leukaemia
Point mutation
What mutation in transcriptional activators (a nuclear regulatory protein) causes
Burkitt lymphoma
What type of mutation are cell cycle regulators Cyclin D and CDK4 susceptible to?
AmplificationCyclin D also susceptible to translocation
What type of cancer can a mutation in Cyclin D cause?
Translocation - mantle cell lymphoma Amplification - breast, liver, oesophageal
What type of cancer does a mutation in cyclin dependant kinase cause?
melanoma, sarcoma
What are the mechanisms of viral carcinogenesis?
Virus genome inserts near a host proto - oncogeneViral promoter or other transcription regulator causes proto-oncogene over expressionRetroviruses insert oncogene into host DNA causing cell division.
Chemical carcinogenesis involves adduct formation, what does this lead to?
Activation of oncogenes and suppression of anti-oncogenes
What is a neoplasm?
A new and abnormal growth of tissue in the body.
What is the function of the p16 protein?
It is an inhibitor of the CDK’s which are involved in the phosphorylation of the of the pRB - progression from G1 to S phase
What happens when pRB is bound to E2F?
The complex acts as a growth suppressor - prevents progression through the cell cycleWhen unbound - no inhibition exists - progression is possible.
