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Basic Science Flashcards

1
Q

Differences between oncogenes and tsgs

A

Oncogene mutations at specific hot spots- TSG mutations throughout gene
Oncogene almost always missense and only one allele affected
TSG both alleles affected so get loss of heterozygosity

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2
Q

Which mutations are mutually exclusive with BRAF mutations?

A

KRAS

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3
Q

The two most commonest mutated oncogenes in human cancer?

A

PI3KCA

KRAS

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4
Q

What happens when CDK4 phosphorylates Rb protein?

A

Lowering of transcription factors essential for progression of cell cycle

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5
Q

What is senescence?

A

Permanent arrest of cell division

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6
Q

What is microRNA?

A

RNA 19-24 nucleotides long

Affect gene expression and protein translation

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7
Q

What does the INK4 family do in relation to the cell cycle?

A

Inhibits it!

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8
Q

What is a proto-oncogene?

A

A normal genetic element in a human which is normal and is found replicated in a virus which can cause malignant transformation
It seems likely that the oncogene went from the eukaryote to the virus

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9
Q

What are the three major DNA checkpoints?

A

G1/S
G2/M
S-phase

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10
Q

What is microRNA?

A

RNA 19-24 nucleotides in length
Affects gene expression and protein translation
Participates in processes like apoptosis
Can look at miRNA arrays and correlate with clinical things like survival!

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11
Q

What is the peptidome?

A

The low molecular weight part of the proteome
Peptides or protein fragments less than 50,000 daltons
Secreted from tumours
Float around circulation bound to carrier proteins
Looking into whether the patterns of the peptides can correlate with clinical things

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12
Q

Which genetic familial cause of CRC is associated with resistance to 5FU?

A

HNPCC

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13
Q

Lifetime risk of CRC with HNPCC?

A

60-80%

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14
Q

What is the prognosis like for CRC with MSI?

A

Favourable

But potentially associated with resistance to 5FU

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15
Q

What kind of drug is azacitidine?

A

DNA hypomethylating agent

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16
Q

Which cell type does neuroblastoma arise from?

A

Primitive sympathetic nervous system cells

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17
Q

Malignancy of Schwann cells?

A

Oligodendroma

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18
Q

What is Z line in oesophagus?

A

Border between squamous and glandular epithelium - looks like bright red dots on endoscopy

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19
Q

What is Philadelphia chromosome?

A

T(9;22) BCR-ABL fusion protein

If present in ALL it is a poor prognostic factor

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20
Q

Ames test

A

Tell how mutagenic something is
Use salmonella
See how quickly salmonella mutates in presence of mutagen

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21
Q

The hallmarks of cancer (six) plus two enabling and two emerging

A 
Independence from growth signals 
Inhibition growth inhibitory signals 
Unlimited replicatory potential 
Evasion of apoptosis 
Angiogenesis 
Invasion and metastasis 
enabling : genome instability and mutation and tumour promoting inflammation 
Emerging:- evading immune destruction and disregarding cellular energetics
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22
Q

What are the stages of the cell cycle?

A 
G0
G1
S
G2 
M
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23
Q

What are CDKs?

A

Cycline dependent kinases have to bind cyclin to be activated

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24
Q

When in the cell cycle are the major DNA damage checkpoints?

A

G1 to S (before make DNA)
During S
G2 to M (before start mitosis)

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25
What is the R point in the cell cycle?
The restriction point (R) is a point in G1 of the animal cell cycle at which the cell becomes “committed” to the cell cycle and after which extracellular proliferation stimulants are no longer required.
26
Does TGF beta promote cell cycling or cause cell cycle arrest?
Cell cycle arrest. Cell is reponsive to TGF beta signalling before the R point is reached in G1- after that the cell is committed to completing the cell cycle
27
What is the effect of having mutated and non functioning Rb?
Mutated dysfunctional Rb can't bind to E2F. The E2F is free to activate transcription of genes that are needed to enter S phase IE unprogrammed cell division
28
What are telomeres made from?
Repetitive DNA sequences and associated proteins called the SHELTERIN complex
29
What is telomerase?
Makes your telomeres longer by adding nucleotides
30
What is a reverse transcriptase?
An enzyme that makes DNA from RNA
31
What are the two pathways of apoptosis called?
Intrinsic - internal chemical/physical damage eg DNA damage or oxidative stress. Mediated by the mitochondria Extrinsic -extra cellular signals called death factors
32
What are caspases?
Cysteine rich aspartase proteases | They are important in both the intrinsic and extrinsic apoptosis pathways
33
Which of the apoptosis pathways is mediated by the mitochondria
Intrinsic
34
Describe the extrinsic pathway of apoptosis?
Death factors bind to death receptors inducing conformational change of Intracellular domain and oligodimerisation. Conformational change exposes DEATH domains on their tails Intracellular proteins FADD and TRADD bind to them These proteins attract pro-caspase 8 start the caspase cascade
35
Name two main activators of angiogenesis | and four inhibitors
2 Activators VEGF and FGF (il 6 and 8) | 4 Inhibitors Thrombospondin, interferon, angiostatin, endostatin
36
Which VEGF is bound by bevacizumab?
VEGF a
37
What do angiopoeitins bind to and what is their job?
Angiopoeitins bind to TIE receptors | Stabilise developing blood cells
38
What is the role of Flip in the apoptosis pathway?
It stops apoptosis by binding to the Intracellular protein FADD (which in turn is the one that normally binds to death receptors)
39
What is apoptosis?
Efficient programmed cell death where the cell swiftly shrinks, blebbing of the plasma membrane, chromatin condensation, intranucleosomal dna fragmentation. The cell corpse is then engulfed by other cells.
40
Name two gene mutations that help evade apoptosis?
P53 | BCL-2
41
What is the function of bcl2
In mitochondria it suppresses apoptosis by inhibiting BAC And BAX BAC and BAX are involved in apoptosis by when they are activated by DNA damage (via p53) they recruit SMAC and cytochrome c activating the caspase pathway
42
What is the Warburg effect?
Cancer cells seem to prefer aerobic glycosis to aerobic respiration even though aerobic respiration actually generates more ATP per molecule of glucose This is despite the fact that cancer cells have normally functioning mitochondria
43
Which malignancy has c-myc amplification?
Small cell lung cancer, 10% of cases | translocation involving myc found in the majority of Burkitts lymphoma
44
What is c-myc?
A gene that codes for a transcription factor
45
How do the names of antibodies tell you their origin?
``` O= murine Xi= chimeric eg cetuximab, rituximab Zu= humanised eg trastuzumab, bevacizumab, Alemtuzumab, pertuzumab Mu= fully human eg panitumumab ```
46
What is NF kappa B?
A transcription factor
47
Name the two major mismatch repair mechanisms of the cell
Nucleotide excision repair | Base excision repair (PARP involved in this)
48
How are double stranded DNA breaks repaired?
Homologous recombination
49
What is the DNA repair problem in Xeroderma pigmentosum?
NER nucleotide excision repair
50
What is the DNA repair problem in Lynch syndrome?
Mismatch repair
51
What is the DNA repair problem in Bloom syndrome?
Helicase deficiency
52
What does aurora B kinase do?
Helps sister chromatids to separate
53
What is the difference between cell quiescence and senescence?
In cultured cells Senescence is permanent - caused by serious stuff like prolonged DNA damage, telomere shortening or oncogene activation Quiescence is temporary- can re enter the cell cycle. Usually if cell is starved, high density growth etc it goes into quiescence
54
What are cyclins?
The positive regulatory subunits of cyclin dependent kinases
55
Which cyclin and CDK are responsible for getting cells into and out of mitosis?
CDK1 and cyclin B
56
What happens to levels of cyclins during the cell cycle?
Fluctuate. Hence why called cyclins | Level of CDKs does not fluctuate during the cell cycle
57
Which cyclin is the first one to rise in the cell cycle during G1?
``` Cyclin D (dares to go first!) Associates with CDK4/6 to drive cell through G1 ```
58
What is the purpose of the G1 checkpoint?
Cell cycle arrest if there is DNA damage- don't want it to be replicated if going into S phase
59
What are the 4 mechanisms of CDK regulation?
Association with cyclins Association with CDK inhibitors Phosphorylation : can be both positive and negative
60
How are levels of cyclins regulated?
``` Cyclin gene transcription Protein degradation (by the proteasome) ```
61
Name the two main families of CDK inhibitors?
P16 INK family | P21 (Cip/Kip) family
62
What is the role of Rb in cell cycle progression?
RB regulates the transition from G1 to S phase | Normally RB binds E2F sequestering it and stopping it interacting with transcription factors
63
Mutations in the NBS1 gene result in which syndrome? What malignancy is more common?
Nijmegen breakage syndrome 1 Increased risk of NHL Microcephaly
64
What is type 1 cell death?
Apoptosis
65
What are the three ligands of the death receptor pathway
TNF alpha Fas TRAIL
66
What percentage of tumour cells can give rise of metastasis?
Less than 0.01%
67
Where is CXCR4 seen and what does it do?
Expressed on the surface of circulating tumour cells Interacts with CXCL12 expressed on certain organs eg LN, liver, lung bone Involved in metastasis

Basma Medical Oncology (26 decks)

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