Cancer 4 Flashcards

1
Q

What are the 3 classes of genes implicated in cancer?

(3 marks)

A
  • Proto-oncogene
  • Tumour suppressor genes
  • Caretaker genes
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2
Q

What do proto-oncogenes do?

(4 marks)

A
  • Promote cell proliferation and cell survival
  • Can turn oncogenic
  • Gain of function mutation - enhanced normal growth, converts proto-oncogenes to oncogenes
  • Only need one copy of gene to have dominant effect and drive cell towards cancer
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3
Q

What happens in cancer when you get a mutation in the coding sequence?

(1 mark)

A

Protein produced is hyperactive/ permanently active

e.g. Ras is mutated in this way in 70% of human tumours

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4
Q

What happens in gene amplification in cancer?

(2 marks)

A
  • Gene is still normal but too much of normal gene is produced
  • e.g. breast cancer get extreme enahancement of Her2 gene which promotes cell proliferation
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5
Q

What happens in chromosome rearrangement in cancer?

(2 marks)

A
  • Rearrangement in chromosome causes a strong promoter nect to a gene that shouldn’t be overexpressed e.g. BCL2 gene overexpressed = antiapoptotic
  • Or translocation between 2 chromosomes - fusion gene or protein produced (hyperactive fusion protein) e.g. leukaeimia
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6
Q

What does a mutation in growth inhibitory proteins cause in cancer?

A

Loss of function - growth is unregulated

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7
Q

In a recessive mutation of growth inhibitory proteins what happens?

(2 marks)

A
  • Loose 2 copies of TS gene before pathological effect is seen e.g. p10, p53 or the retinoblastmoprotein
  • This allows cells to grow with damaged DNA and can inhibit more processes
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8
Q

What are the different genetic events that can cause a loss of function of tumour suppressor genes?

(5 marks)

A
  • Loss of whole chromosome
  • Regional deletion (containing normal gene)
  • Chromosome rearrangement
  • Mutation in coding sequence: protein non-functional p10 used to regulate Akt signalling
    • p10 dephosphorylates PIP3 which causes PIP2 to shut down Akt signalling
  • Epigenetic changes causing gene silencing
    • remodelling complex e.g. SWI/SNF
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9
Q

What are inherited tumour suppresor genes - give an example.

(2 marks)

A
  • Offspring can inherit mutation of one allele of tumour suppresor - has predisposition for tumours e.g. hereditary retinoblastoma: inherited mutation in one allel for RB TS gene (essential for regulating key part of cell cycle)
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10
Q

What is familial adenomatous polyposis (FAP) and Adenomatous polypsis coli (APC)?

(3 marks)

A
  • Loss of tumour suppressor gene (both)
  • APC: loss leads to polyps in in epithelial lining of colon
  • Patients w/ polyps are monitored and polyps removed regularly
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11
Q

What is a caretaker gene mutation?

(1 mark)

A
  • Cell mutated which leads to an accelerated conversion of normal cell to neoplastic cell
  • Loss of function mutation
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12
Q

What do caretaker genes do?

(5 marks)

A
  • DNA repair or prevention of DNA damage
  • Different DNA mechanisms for different damages:
    • DNA mismatch repair
    • Nucleotide excision repair
    • Double stranded DNA breaks
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13
Q

What is the name of the inhertied gene that makes you 80-90% more likely to develop breast cancer?

(1 mark)

A

Braca gene

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14
Q

What intermediate is NOT formed in radiolysis?

(1 mark)

A

Water

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15
Q

Why may foods act as a cancer causative factor?

(2 marks)

A

May carry Benzo[a]pyrene - most frequently associated carcinogens with lung cancer

Cooked/ smoked meats

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16
Q

What are cyclin dependent kinases?

(1 mark)

A

Serine threonine kinases

17
Q

At what stage in the cell cycle do cyclins appear?

(4 marks)

A
  • Some only in G phase (G1 cyclins)
  • Some in late G1 and early S phase (G1/s cyclins)
  • Some in S phase (S phase cyclins)
  • Some in M phase (M phase cyclins)
18
Q

What is the main role for CDK activity?

(1 mark)

A
  • Regulating cell cycle events and can be enhanced or inhibited by phsophorylation
19
Q

How does the cell cycle allow for DNA repair?

(2 marks)

A
  • G2 checkpoint blocks entry into M phase thats incured DNA damage in previous phases or not properly completed S phase
  • Allows for DNA repair
20
Q

How can you regulate CDK?

(4 marks)

A
  1. Association with cyclins
  2. Association with CDK inhbitors
  3. Addition of phosphate groups that regulate the activity of CDK
  4. Addition of phosphate groups that inhibit CDK activity
21
Q

Give a few examples of CDK inhibitors?

(4 marks)

A

p15, p16, p21 and p27

22
Q

What are some of the controls put in place to control the cell cycle?

(3 marks)

A
  • Regulated by feedback by processes in that phase
  • Checkpoint in mitosis in M phase - checks chromosomes are properly attached to the spindle
  • G1 checkpoint - controls transition from G1 phase to S phase
23
Q

What does tumour suppressor protein RB do?

(3 marks)

A
  • Acts as a molecular link for G1 to S transition
  • Prevents cell from going to S phase bound to TF, E2F so no transition past the start
  • Inactivation RB promotes chromosomal instability, angiogenesis and increased expression of E2F
24
Q

What is CDK 4 inhibited by?

(1 mark)

A

p16

25
Q

What happens cyclin D is bound to CDK 4?

(2 marks)

A
  • Phosphorylation of RB which then can’t hold onto E2F
  • So can go and transcribe genes to push past G1 checkpoints
26
Q

How does deregulation of cell division and checkpoints occur?

(4 marks)

A
  • Overexpression of proto-oncogene for cyclin D by gene amplification (gene for ti is proto-oncogene)
  • Loss of TS genes for p16 CDK inhibitor - due to asbestos exposure
  • Loss of TS gene for RB
  • Viruses make proteins that affect signalling molecules e.g. HPV makes protein that binds to RB and degrades it
27
Q

What does p53 do and whath happens when there are mutations to it?

(5 marks)

A
  • Binds to ~300 genes infleunces gene transcription
  • Issues in checkpointd p53 are stimulated to produce p26 and p27 - CDK inhibitors put cell in arrest
  • In response to radiation, drugs, carcinogen induced DNA damage - puts cell in apoptosis
  • Nearly all mutations of p53 found in DNA binding domain
  • In low levels of p53, induce antioxidant activity which decreases levels of ROS and subsequent DNA damage