Hallmarks of Cancer Flashcards
List the 6 major hallmarks of cancer.
Sustaining proliferative signalling Evading Growth suppressors Resisting cell death Angiogenesis Replicative immortality Invasion and metastasis
Give an example of a gene required for apoptosis.
p53
Over-expression of which anti-apoptotic protein contributes to resistance of cell death?
Bcl2
Which translocation leads to over-expression of Bcl2 (follicular lymphoma)
IGH on c14 and Bcl2 on c18
What does chronic BCR activation lead to?
Excessive proliferation and B-cell non-Hodgkin lymphoma
Does removal of H. pylori cause regression of the gastric B-cell lymphoma?
Yes, dependent on the signalling
Does removal of gluten cause retraction of the enteropathic T-cell lymphoma?
No
What is the mechanism of p53 action?
Initials growth arrest for DNA repair to occur. If DNA is not repaired, apoptosis occurs.
What is the mechanism of Rb function?
Regulated G1 checkpoint via E2F transcription factors.
Inhibits CDK-cyclins
When is Rb inactive?
When it is phosphorylated
What is the molecular basis of mantle cell lymphoma?
t(11;14) translocation
Cyclin D is translocated onto immunoglobulin heavy chain enhancer elements
In what percentage of human cancers is TERT activated?
85%
Is cycle translocation alone sufficient to cause lymphoma?
No, eventually the cells would stop replicating and die. TERT is activated too.
What are the four emerging hallmarks of cancer?
Deregulating cellular energetics
Avoiding immune destruction
Genome instability and mutation
Tumour-promoting inflammation
What is the function of isocitrate dehydrogenase (IDH)?
Convert citrate to alpha-ketogluterate
What is the consequence of IDH mutation?
Mutated IDH produces alpha-hydroxygluterate, breaking the CAC and causing the Warburg effect
DNA methylation is affected
What gene is amplified in Hodgkin lymphoma?
PD-L1 and PD-L2, they exhaust T cells
What does Venetoclax target?
BCL2 (apoptosis inhibitor)
What does Ibrutinib target?
BCR signalling by inhibiting BTK
What is the consequence of chronic BCR over-activation?
Excessive proliferation and non-Hodgkin lymphoma
If H. pylori removed, does gastric B cell lymphoma regress?
Yes, it is dependent on the signalling from H. pylori
If gluten is removed, does the enteropathic T-cell lymphoma regress?
No
Which cell cycle checkpoint is regulated by Rb?
G1
Explain how Rb functions
Inhibited by phosphorylation
Regulates G1 checkpoint via E2F transcription factors
Inhibits CDK-cyclins
How does p53 function?
Induces growth arrest for DNA repair to occur. If repair cannot occur, apoptosis occurs.
