Cancer 2 - Oncogenes and Tumour Suppressors Flashcards

1
Q

In the cell cycle, what is the G0 phase

A

The quiescent phase - cell not replicating

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2
Q

What occurs during the G1 phase?

A

Cell ensuring it has enough nutrients, nucleotides, etc for replication

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3
Q

What happens at the end of G1, and why?

A

Growth arrest (checkpoint) - ensures genetic fidelity of the cell

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4
Q

Name 3 proteins that accumulate and are destroyed during the cell cycle

A
  1. Cyclins
  2. Cyclin-dependant kinases
  3. Cyclin-dependant kinase inhibitors
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5
Q

What does permanent cyclin activation do?

A

Ceases growth arrest and causes cell to drive through checkpoints

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6
Q

What can a mutation to a proto-oncogene do?

A

Cause it to become an oncogene, whereby the protein product does not respond to control influences

Proto-oncogene can become an oncogene through a single mutation

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7
Q

4 ways in which oncogene activation can occur

A
  1. Mutation in coding sequence
  2. Gene amplification
  3. Chromosomal translocation
  4. Insertional mutagenesis
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8
Q

What may cause gene amplification to occur?

What can having multiple copies of a gene cause?

A

Problems with polymerase protein may cause gene amplification

Multiple copies of a gene = overproduction of gene product

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9
Q

What are chimeric genes?

A

Genes formed by combining parts of 1/more coding sequences - resulting in new genes (e.g. swapping tips of chromosomes)

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10
Q

What happens in Burkitts lymphoma

A

One of the translocated pieces of DNA is a promotor which leads to up regulation of the other gene portion (i.e. promotor acts as a strong enhancer)

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11
Q

Give an example of when a fused gene can form an abnormal protein?

A

Philadelphia chromosome in CML

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12
Q

Which 2 chromosome segments are translocated to form the Philadelphia chromosome?

A

Chr 9 - ABL

Chr 22 - BCR

Results in BCR-ABL fusion gene on Chr 22 - development of cancer

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13
Q

Why are proto-oncogenes critical gene targets?

A

They regulate signal transduction pathways

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14
Q

What is Ras and what does it normally do?

A

It is part of a pathway involved in producing gene regulatory pathways - Ras part of a family of membrane bound GTP-ases important in cell proliferation.

It binds to GTP and activates the kinase cascade - it is switched off when GTP is dephosphorylated to GDP

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15
Q

What cascade is Ras part of?

A

Mitogen activated protein kinase cascade (MAPK)

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16
Q

What happens in mutant Ras?

A

Mutant Ras fails to dephosphorylate GTP - so no GDP so Ras remains active

17
Q

What are the main functions of tumour suppressor genes?

A

Regulate cellular proliferation and maintain cell integrity

18
Q

How many copies of a TSG does a cell have?

A

2 - mutation/deletion of 1 TSG is usually insufficient to cause cancer

19
Q

What are the features of inherited cancer susceptibility (non functioning TSGs)

A
  1. Family history of related cancers
  2. Early onset
  3. Bilateral tumours in paired organs
20
Q

Give an example of an inherited cancer?

A

Retinoblastoma

21
Q

What mutation causes retinoblastoma

A

RB1 TSG on chromosome 13q14

22
Q

What does RB1 encode?

A

Nuclear protein involved in regulating cell cycle

23
Q

What is the overall function of TSGs?

A

To suppress the neoplastic phenotype

24
Q

When p53 is bound to _____ it is inactive

A

MDM2

25
Q

What is p53

A

It is a TSG but it requires only a mutation of a single copy to get dysregulation - p53 mutants act in a dominant manner

26
Q

What does p53 do?

A

It is triggered by cellular stressors (physiological and severe)

It is involved in regulating p53 target genes and protein-protein interactions

27
Q

How is p53 stabilised so it isn’t degraded quickly and can exert its effects

A

It is phosphorylated

28
Q

What can mutation of the APC tumour suppressor gene cause?

A

Familial Adenomatous Polyposis Coli (FAPC)

29
Q

What causes FAPC

A

Deletion in 5q21 - results in loss of APC tumour suppressor gene

30
Q

Are the polyps cancerous in FAPC

A

NO

But there is a 90% risk of developing colon cancer

31
Q

How does APC protein prevent uncontrolled growth?

A

Helps control Beta-catenin activity and also is involved in the WNT signalling pathway

32
Q

What 2 factors may cause polyps to develop into adenomas?

A

DNA hypomethylation & K-ras mutation

33
Q

Both TSG and oncogenes are involved in development of colorectal cancer

A
APC gene (TSG)
K-ras (oncogene)
34
Q

Are TSG or oncogenes caused by deletion/mutations?

A

TSG inactivated by deletions/mutations

Oncogenes caused by specific translocations / point mutations