Wiki Flashcards Tumour Suppressor Genes

Question 1

What is a TSG?

Answer 1

A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.

Question 2

TSG can be grouped into categories. What are some examples?

Answer 2

Caretaker genes,
Gatekeeper genes
Landscaper genes

Question 3

What does the ‘two hit hypothesis’ mean in the context of TSG?

Answer 3

Unlike oncogenes, tumor suppressor genes generally follow the “two-hit hypothesis,” which implies that both alleles that code for a particular protein must be affected before an effect is manifested. This is because if only one allele for the gene is damaged, the second can still produce the correct protein. In other words, mutant tumor suppressors’ alleles are usually recessive whereas mutant oncogene alleles are typically dominant.

Question 4

What is one well known notable example to the ‘two-hit’ rule?

Answer 4

p53. Tetramer.
p53 mutations can function as a “dominant negative,” meaning that a mutated p53 protein can prevent the function of normal protein from the un-mutated allele.

Question 5

What is haploinsufficiency?

Answer 5

Haploinsufficiency is a mechanism of action to explain a phenotype when a diploid organism has lost one copy of a gene and is left with a single functional copy of that gene. Haploinsufficiency is often caused by a loss-of-function mutation, in which having only one copy of the wild-type allele is not sufficient to produce the wild-type phenotype. It occurs when an organism has a single functional copy of a gene, and that single copy does not produce enough product to display the wild type’s phenotypic characteristics.

Question 6

What are two examples of TSG will display haploinsufficiency?

Answer 6

PTCH (Medulloblastoma)

NF1 (Neurofibroma)

Question 7

PTCH is an example of what?

Answer 7

TSG that displays haploinsufficiency and causes medulloblastoma.

Question 8

What does PTCH cause?

Answer 8

Medulloblastoma, example of a TSG that displays haploinsufficiency WRT two hit.

Question 9

What is NF1 an example of?

Answer 9

TSG that displays haploinsufficiency and causes Neurofibroma.

Question 10

What does NF1 cause?

Answer 10

Neurofibroma, TSG/haploinsufficiency

Question 11

What was the first TSG discovered?

Answer 11

pRB - retinoblastoma, binds E2F normally but after GF activation and phosphorylation by CDK4/6 releases E2F which can act as a transcription factor to cause cancer.

Question 12

What are five examples of the functions tumour suppressor proteins are commonly involved with?

Answer 12

1. Repression of genes that cause cell cycle progression.
2. Coupling the cell cycle to the health of the DNA: if there is damaged DNA in the cell, it should not divide until this is repaired.
3. If the DNA damage is not repaired then the cell should initiate apoptosis to remove the threat.
4. Metastasis suppressors are proteins that are involved in cell adhesion and which prevent tumour cells from dispersing, block loss of contact inhibition, and inhibit metastasis.
5. DNA repair proteins. HNPCC, MEN1 and BRCA.

Question 13

HNPCC, MEN1 and BRCA are examples of what type of TS?

Answer 13

They are DNA repair proteins - mutations in these increase the mutation rate from decreased DNA repair.

Question 14

p53 tumour-suppressor protein is encoded by

Answer 14

TP53 gene.

Question 15

The TP53 gene codes for what

Answer 15

p53 TS protein.

Question 16

Homolygous loss of p53 is found in 65% of ______ cancers.

Answer 16

Colon

Question 17

Li-Fraumeni syndrome (LFS) is associated with inherited abnormalities of the ___ gene?

Answer 17

p53.

This leads to increased risk of developing various types of cancers.

Question 18

Among the most frequently mutated genes are components of the SWI/SNF chromatin remodelling complex, which are lost in about __% of tumours.

Answer 18

20%

Question 19

Among the most frequently mutated genes are components of the __________ chromatin remodelling complex, which are lost in about 20% of tumours.

Answer 19

SWI/SNF

SWItch/Sucrose Non-Fermentable.

Question 20

pVHL, APC, CD95, ST5, YPEL3, ST7 and ST14 are examples of what?

Answer 20

TSGenes.

Question 21

What is the SWI/SNF chromatin remodelling complex?

Answer 21

A chromatin remodelling complex, which is lost in about 20% of tumours.

Question 22

The p27Kip1 cell-cycle inhibitor is an example of what?

Answer 22

A TSG that displays haploinsufficiency.

Mutation to a single allele causes increased carcinogen susceptibility.

Question 23

What role does p27Kip1 play?

Answer 23

It inhibits the cell-cycle - a mutation in a single allele causes an increased carcinogen susceptibility.

TSGene which displays haploinsufficiency.

Question 24

What do mutations in a single allele for p27Kip1 produce?

Answer 24

It inhibits the cell-cycle - a mutation in a single allele causes an increased carcinogen susceptibility.

TSGene which displays haploinsufficiency.

Question 25

Why is noninherited retinoblastoma rare?

Answer 25

Noninherited retinoblastoma is rare because its development requires two independent somatic mutations to inactivate both normal copies of Rb in the same cell.

Question 26

The Rb protein is a key target for the oncogene proteins of several DNA tumour viruses such as ________

Answer 26

SV40.

Question 27

What is familial adenomatous polyposis?

Answer 27

Rare form of hereditary colon cancer caused by mutations to the APC TSP gene.

People develop hundreds of benign colon adenomas (polyps), some of which almost inevitably progress to malignancy.

Question 28

What two TSGs are responsible for 5%-10% of breast cancers? (inherited)

Answer 28

BRCA1

BRCA2

Question 29

How does the PTEN TSG display antagonism between oncogene and TSG products?

Answer 29

PTEN protein is a lipid phosphatase that dephosphorylates the 3 position of phosphatidylinositides.

By dephosphorylating PIP3, PTEN antagonises the activities of PI 3-kinase and Akt, which act as oncogenes by promoting cell survival.

Conversely, inactivation or loss of the PTEN TSP can contribute to tumour development as a result of increased levels of PIP3, activation of Akt and inhibition of apoptosis.

Question 30

What is an example of a TSG that mutations of are associated with the rare inherited form of colon cancer, familial adenomatous polyposis?

Answer 30

APC gene

Question 31

What is SV40?

Answer 31

A DNA tumour virus that has oncogene proteins which target the Rb protein not the GENE.

Question 32

How does inactivation or loss of the PTEN tumour suppressor protein contribute to tumour development?

Answer 32

Increased levels of PIP3, increased activation of Akt and inhibition of apoptosis.

Question 33

In the Hh pathway, how are the Smoothened receptor and Patched receptor different?

Answer 33

Smoothened = oncogene in basal cell carcinoma.

Patched (negative regulator of Smoothened) is a tumour suppressor gene