Oncogenes And Tumour Suppressor Genes Flashcards

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1
Q

Function of a proto-oncogene?

A

Control differentiation and proliferation to regulate homeostasis

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2
Q

What are Ras - tumour suppressor or oncogenes?

A

Oncogenes

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3
Q

How are Ras genes activated and what do they cause?

A

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

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4
Q

What happens if there is a mutation to the Ras protein?

A

Switched on all the time causing constant proliferation. Doesn’t need the tyrosine kinase receptor to activate it.

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5
Q

Why are Ras mutations easy to detect?

A

Only nine bases can be changed

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6
Q

What kind of cancers are Ras mutations common in?

A

Epithelial cancers such as

  • colon
  • bladder
  • lung
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7
Q

Where can mutations be found for Ras?

A

Codons 12, 13 and 61

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8
Q

How can the type of Ras mutation be an indicator of prognosis in colorectal cancer?

A

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

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9
Q

What is insertional mutagenesis?

A

When a DNA virus incorporates a viral oncogene into the host DNA.

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10
Q

What can cause insertional mutagenesis?

A

HPV 16 and 18 - cervical cancer

Hep B - hepatocellular cancer

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11
Q

What is a chromosomal translocation?

A

When a fragment of one chromosome attaches to another non-homologous chromosome

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12
Q

Give some examples of chromosome translocations that can lead to cancer

A

9;22 - chronic myeloid leukaemia leading to abnormal tyrosine kinase activity (Philadelphia chromosome)

8;14 - burkitt’s lymphoma leading to constitutive MYC expression

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13
Q

What is an example of gene amplification and in which cancer is it seen?

A

Human epidermal growth factor receptor 2 (HER-2).
Amplified and over-expressed in 20-30% of breast cancers
Linked to poor prognosis

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14
Q

What can gene amplification be detected by?

A

FISH

Immunohistochemistry

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15
Q

What can breast cancer with HER-2 amplification be treated with?

A

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

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16
Q

What is seen when HER-2 positive cells are stained?

A

Dark membranes because HER-2 is found on the membrane

17
Q

Normal function of tumour suppressor genes?

A

Maintain genetic stability by

  • DNA repair
  • carcinogen detoxification
  • cell cycle control
  • apoptosis
  • senescence
18
Q

What causes senescence?

A

Telomeres shortening

19
Q

What are the different types of retinoblastoma?

A

Familial - seen bilaterally - 40%

Sporadic - unilateral - 60%

20
Q

What is the two hit hypothesis for retinoblastoma?

A

Tumour triggered by two mutation events

  • first recessive mutation inherited and seen in all cells
  • only need one more mutational event to affect the other allele to initiate a tumour
21
Q

Why is sporadic retinoblastoma normally only seen unilaterally?

A

Need two hits and the chances of two hits happening in the same cell is very small

22
Q

What makes a cell population more heterozygous?

A

The more alleles for a gene there are

23
Q

What is loss of heterozygosity?

A

When there is a mutation leading to deletion of an allele, can cause LOH.

24
Q

Where does LOH normally involve on the DNA?

A

The flanking chromosomal region near the 5’ end

This area of DNA is not normally transcribed into RNA

25
Q

Why can LOH lead to cancer?

A

Only have one remaining copy of a tumour suppressor gene which can be inactivated by a point mutation, leaving no tumour suppressor gene.

26
Q

What is the most commonly mutated gene in cancer?

A

p53 (seen in 50% of cancers)

27
Q

What is the function of p53?

A

Cell cycle G1 arrest in response to DNA damage

Can trigger both cell differentiation and apoptosis.

28
Q

What is DNA CpG methylation?

A

Addition of methyl groups to cytosine (where cytosine is found next to a guanine base)

29
Q

What can promoter methylation cause?

A

Tumour suppressor gene inactivation - silences the gene

30
Q

When does promoter methylation normally arise?

A

Ageing of cells

31
Q

What possible mutations can you get to genes?

A
Deletion of base pairs, genes, chromosomes 
Insertion of base pairs or viruses
Substitution of base pairs
Amplification of genes/chromosomes 
Translocation of a chromosome