Cancer I

Question 1

The incidence rate of cancer is consistent with how many required independent mutations?

Answer 1

5-6

Question 2

Describe germline mutations.

Answer 2

Germline mutations are present in egg or sperm therefore are heritable and affect all cells in offspring. These can cause cancer family syndromes.

Question 3

Describe somatic mutations.

Answer 3

Somatic mutations occur in non-germline tissues and are nonheritable.

Question 4

Genes which encode proteins which stimulate cell proliferation are known as…

Answer 4

Proto-oncogenes

Question 5

What are normal cellular proto-oncogenes involved in?

Answer 5

Proto-oncogenes are involved in cell growth and/or cell division

Question 5

Genes which encode proteins which prevent cell proliferation as known as…

Answer 5

Tumour suppressor genes

Question 6

What are oncogenes?

Answer 6

Oncogenes are proto-oncogenes which have been activated by a mutation or overexpression, resulting in a dominant gain of function phenotype.

Question 7

How many proto-oncogenes be turned into oncogenes?

Answer 7

• Point mutations: deletion or point mutations in the coding sequence can cause a hyperactive protein to be made in normal amounts
• Gene amplification: can cause normal proteins to be greatly overproduced
• Chromosomal rearrangement: regulatory sequence may cause overproduction of normal protein or fusion can greatly overproduce fusion proteins

Question 8

Give an example of a point mutation known to cause cancer in humans.

Answer 8

More than 30% of all human cancers are driven by mutations in the Ras gene which leads to uncontrolled growth, proliferation and migration. This is most common in pancreatic, colorectal and lung cancers.

Question 9

Give an example of an oncogene which belongs to the growth factor category, and describe its function.

Answer 9

Platelet-derived growth factor (PDGF) increases cell proliferation.

Question 10

Give an example of an oncogene which belongs to the receptor tyrosine kinase category, and describe its function.

Answer 10

Epidermal growth factor receptor (EGFR) is used to transduce signals for cell proliferation.

Question 11

Give an example of an oncogene which belongs to the signal-transducing proteins category, and describe its function.

Answer 11

Ras is involved in signalling.

Question 12

Give an example of an oncogene which belongs to the transcription factor category, and describe its function.

Answer 12

Myc is used to regulate transcription of genes which induce cell proliferation.

Question 13

Tumour suppressor genes are needed to prevent inappropriate proliferation. What type of mutation can they undergo?

Answer 13

Mutations of tumour suppressor genes are recessive, loss of function.

Question 14

Most cancers result from mutations in cellular genes. What two types of cancer can be found?

Answer 14

1) Sporadic: more frequent, no hereditary cause
2) Familial: less frequent, hereditary

Question 15

What does Knudson’s “Two-Hit Hypothesis” state?

Answer 15

The first hit in the development of a familial tumour occurs in the germline in a cancer susceptibility gene while the second hit occurs somatically in another allele of the same gene. This is because two mutations are required for loss of tumour suppressor function.

Question 16

True or false: Loss of function of a single copy of tumour suppressor gene, Retinoblastoma (Rb1), is not enough to cause a tumour.

Answer 16

True, this is not enough to cause a tumour as both copies would have to be mutated since this is recessive however one mutation is a key step in the development of a tumour of the retina.

Question 17

Sporadic retinoblastoma makes up 60% of retinoblastoma cases. How and in whom does it manifest?

Answer 17

Sporadic retinoblastoma develops in children with no family history and occurs in one eye.

Question 18

Hereditary retinoblastoma makes up 40% of retinoblastoma cases. When, how and in whom does it manifest?

Answer 18

Hereditary retinoblastoma onset is typically earlier than in sporadic cases. It follows consistent pedigrees with siblings and offspring often developing the same type of tumours. It often involves multiple tumours affecting both eyes.

Question 19

In sporadic retinoblastoma cases, what type of mutations are present?

Answer 19

Somatic mutation occurs in two alleles causing single tumours which are unilateral and later onset than in familial cases.

Question 20

In familial retinoblastoma cases, what type of mutations are present?

Answer 20

A tumour suppressor gene containing a germline mutation in one allele is present. A second, somatic mutation in another allele leads to multiple tumours which are bilateral and earlier onset than in sporadic cases.

Question 21

What would happen if someone was homozygous for the retinoblastoma mutant?

Answer 21

This would be lethal at the embryonic stage.

Question 22

What is the function of Rb in the cell cycle?

Answer 22

It is a critical effector of DNA damage checkpoint function which can cause cell cycle arrest at G1 if DNA damage is sensed.

Question 23

How does E2F work with Rb?

Answer 23

Non-phosphorylated Rb binds to E2F. Rb is phosphorylated and releases E2F. E2F migrates into the nucleus to induce transcription. The proteins required for cell cycle progression are produced.

Question 24

p53 is a transcription factor which regulates…

Answer 24

the cell cycle, DNA repair and apoptosis.

Question 25

Name three key cellular processes which tumour suppressors partake in?

Answer 25

The regulation of transcription, DNA repair and cell to cell communication.

Question 26

In the normal cell cycle inhibiting pathway, what is the response to DNA damage?

Answer 26

Protein kinases sense the damage and lead to the activation of p53, altering transcription in the nucleus which leads to production of proteins that inhibit the cell cycle. Damaged DNA is, therefore, not replicated as no cell division occurs.

Question 27

What happens in the mutant cell cycle inhibiting pathway?

Answer 27

p53 is defective or missing. DNA damage is detected by the protein kinases but p53 cannot be activated therefore no inhibitory proteins are produced and the cell cycle continues, leading to increased cell division.

Question 28

Where does breast cancer occur?

Answer 28

Breast cancer occurs in the cells which line the lobules that manufacture milk, or more commonly in the ducts which carry milk to the nipple.

Question 29

Most hereditary breast cancer cases are caused by a mutation in which genes?

Answer 29

Loss of function allele in BRCA1 and BRCA2 which are tumour suppressor genes.

Question 30

How, and in whom, does sporadic breast cancer manifest?

Answer 30

Sporadic breast cancer usually manifests in older woman (when compared to familial). It is usually one tumour in one breast (unilateral).

Question 31

How, and in whom, does familial breast cancer manifest?`

Answer 31

Familial breast cancer occurs in woman who are heterozygous for the BRCA1 mutation. They are often younger than those affected by sporadic breast cancer and often have multiple tumours affecting both breasts (bilateral).

Question 32

What is the function of BRCA1?

Answer 32

BRCA1 is a protein which is required for normal DNA repair. Loss of function mutations can accumulate and cause cancer.