Tumour Suppressor Genes and Clinical Implications

Question 1

In what proportion of cancers is p53 mutated?

Answer 1

p53 is mutated in 50% of cancers.

Question 2

What is the Knudson 2 hit hypothesis?

Answer 2

The Knudson 2 hit hypothesis states that tumor suppressor genes require both alleles to be inactivated in order to cause cancer.

Question 3

With which cancer is the APC tumour suppressor gene associated?

Answer 3

APC is associated with colorectal cancer.

Question 4

With which cancers are BRCA1 and 2 tumour suppressor genes associated?

Answer 4

• BRCA1 is associated with both breast and ovarian cancers.

- BRCA2 is associated with breast cancer.

Question 5

With which cancer is the DPC4 tumour suppressor gene associated?

Answer 5

DPC4 is associated with pancreatic cancer.

Question 6

With which cancer is the INK4 tumour suppressor gene associated?

Answer 6

INK4 is associated with:

1 - Melanoma.

2 - Lung carcinoma.

3 - Brain tumours.

4 - Leukaemias.

5 - Lymphomas.

Question 7

With which cancer is the MADR2 tumour suppressor gene associated?

Answer 7

MADR2 is associated with colorectal cancer.

Question 8

With which cancer is the NF1 tumour suppressor gene associated?

Answer 8

NF1 is associated with neurofibrosarcoma.

Question 9

With which cancer is the NF2 tumour suppressor gene associated?

Answer 9

NF2 is associated with meningioma.

Question 10

With which cancer is the p53 tumour suppressor gene associated?

Answer 10

Remember brain tumours, but p53 is associated with loads of cancers so cba ennit just write down every cancer you can think of.

Question 11

With which cancer is the PTC tumour suppressor gene associated?

Answer 11

PTC is associated with basal cell carcinoma.

Question 12

With which cancer is the PTEN tumour suppressor gene associated?

Answer 12

PTEN is associated with loads of cancers so cba ennit just write down every cancer you can think of.

Question 13

With which cancer is the Rb tumour suppressor gene associated?

Answer 13

Rb is associated with:

1 - Retinoblastoma.

2 - Sarcomas.

3 - Bladder cancer.

4 - Breast cancer.

5 - Lung carcinoma.

Question 14

With which cancer is the VHL tumour suppressor gene associated?

Answer 14

VHL is associated with renal cell carcinoma.

Question 15

With which cancer is the WT1 tumour suppressor gene associated?

Answer 15

WT1 is associated with Wilms tumour (a type of kidney cancer).

Question 16

What type of genetic change most commonly underlies thyroid cancer?

Which signalling pathway is most commonly affected in thyroid cancer?

Answer 16

• Thyroid cancer is most commonly caused by dysregulation of oncogenes rather than dysregulation of tumour suppressor genes.
• Uncontrolled activation of the MAPK (ras/raf/mek/erk) pathway occurs in most thyroid cancers.

Question 17

How do BRAF mutations affect thyroid cancer progression?

Answer 17

BRAF mutations increase the risk of:

1 - Extrathyroidal invasion.

2 - Lymph node metastases.

Question 18

Define anaplastic.

Answer 18

A tumour is anaplastic if it has significantly differentiated from, and has therefore lost the morphological characteristics of, the tissue from which it originates.

Question 19

How do p53 mutations affect thyroid cancer progression?

Answer 19

p53 mutations trigger anaplasia of thyroid cancers.

Question 20

What is Cowden’s syndrome?

What causes it?

Answer 20

• Cowden’s syndrome is an autosomal dominant disorder that increases the risk of developing various cancers.
• It is caused by a germline mutation in p10, a tumour suppressor gene.

Question 21

What is familial adenomatous polyposis?

What causes it?

Answer 21

• Familial adenomatous polyposis is an autosomal dominant condition that increases the risk of developing colorectal cancer.
• It is caused by a biallelic mutation in the MYH gene, a tumour suppressor gene which encodes a glycosylase (remember these are involved in DNA repair).

Question 22

Describe the differences between the pathogenesis of colon cancers that occur on the left side and the right side of the colon.

Answer 22

• Left sided colon cancers are often caused by a loss of heterozygosity (aneuploidy or polyploidy), resulting in loss of APC function.
• Right sided colon cancers are often caused by microsatellite instabilities, resulting in mutation of beta catenin.

Question 23

List 5 genes that can contribute to melanoma formation in order of frequency (from highest to lowest).

Are these genes oncogenes or tumour suppressor genes?

Answer 23

1 - BRAF (an oncogene).

2 - NRAS (an oncogene).

3 - PTEN (a tumour suppressor).

4 - NF1 (a tumour suppressor).

5 - CKIT (an oncogene).

Question 24

List the cell signalling pathways that are affected in melanoma.

Answer 24

Pathways affected in melanoma include:

1 - The MAPK (ras/raf/mek/erk) pathway.

2 - The PI3K/AKT pathway.