CA2: Clinical Cancer Genetics

Question 1

What type of mutations do all cancers have?

Answer 1

All cancers have somatic mutations

Question 2

Changes in the DNA sequence that occur commonly in the population are termed?

Answer 2

Polymorphisms

Question 3

Some individuals carry rare germ lie mutations, what do these do?

Answer 3

Increase the risk of particular cancers from between 5 and >1000 fold

Question 4

Give some examples of inherited cancers? (4)

Answer 4

• Retinoblastoma
• Multiple Endocrine Tumours
• Breast Cancer
• Colon Cancer

Question 5

How many pathways must mutate to create a human tumour cell according to experimental evidence?

Answer 5

Experimental evidence suggests at least four pathways must be mutated to create a human tumour cell

Question 6

What can make a proto-oncogene into an oncogene? (2)

Answer 6

• Mutations

- Increased expression

Question 7

Proteins produced by oncogenes are termed?

Answer 7

Oncoprotein

Question 8

Proto-oncogenes code for protein that help regulate what? (2)

Answer 8

• Cell growth

- Differentiation

Question 9

Name 2 things that proto-oncogenes are often involved in regarding signals?

Answer 9

• Signal transduction

- Execution of mitogenic signals

Question 10

The conversion of a proto-oncogene to an oncogene is termed?

Answer 10

Oncogene activation

Question 11

What do kinases do?

Answer 11

Kinases add phosphate to amino acids like serine and tyrosine

Question 12

What do phosphatases do?

Answer 12

Phosphatases remove phosphate from amino acids.

Question 13

What do cyclins and cyclin-dependent kinases form?

Answer 13

Complexes

Question 14

Explain generally how growth factors instruct cells to synthesise DNA

Answer 14

• Growth factor binds to receptor
• Activation of oncogenes and cascade of events
• Transcription factor activated
• Cyclin d1 transcribed
• cdk4 forms DNA

Question 15

What causes the over-expressed oncogene (MYCgene)?

Answer 15

Chromosome rearrangement

Question 16

In what medical condition is the MYCgene implicated?

Answer 16

Burkitt’s Lymphoma

Question 17

Explain the events causing MYCgene implication

Answer 17

• Chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene
• The MYC gene codes for widely used transcription factors.
• When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates

Question 18

What does the Philadelphia chromosome cause?

Answer 18

Chronic Myelogenous Leukemia

Question 19

Explain the events leading unto the Philadelphia chromosome and what does it code for?

(What chromosomes are involved?)
(What gene is involved?)

Answer 19

• Translocation between chromosome 9 and 22
• Chromosome 22 now becomes the ‘Philadelphia chromosome’ which contains the BCR-ABL gene
• Bcr-Abl codes for a receptor tyrosine kinase, leading to uncontrolled cell proliferation.

Question 20

What are gatekeeper tumour suppressor genes?

Answer 20

Gatekeeper genes that regulate tumour growth by controlling proliferation or promoting cell death

Question 21

What are caretaker tumour suppressor genes?

Answer 21

Caretaker genes are generally DNA repair genes or genes that otherwise protect the genome from acquiring or retaining DNA damage

Question 22

What is the cancer risk increase if a gatekeeper gene is inactivated? Why?

Answer 22

Gatekeeper gene inactivation leads to a very large increase in cancer risk >1000 fold because only one further mutation is required to initiate neoplasia.

Question 23

What is the cancer risk increase if a caretaker gene is inactivated? Why?

Answer 23

Caretaker gene inactivation leads small increase in cancer risk 5-50 fold because up to three further mutations are required to initiate neoplasia

Question 24

What and how many mutations are required for the ATM gene to generate a cancer?

What type of gene is this?

Answer 24

• 1 germ line mutation
• 2 somatic gatekeeper mutations
• 3 in total
• Recessive gene

Question 25

What and how many mutations are required for the BRCA1 gene to generate a cancer?

What type of gene is this?

Answer 25

• 2 somatic gatekeeper mutations
• 2 in total
• Dominant gene

Question 26

pRB gene;

Function?
Which cancers? (2)

Answer 26

• Control of restriction point
• Retinoblastoma
• Osteosarcoma

Question 27

CDKN2A gene;

Function?
Which cancer?

Answer 27

• Control of restriction point

- Melanoma

Question 28

TP53 gene;

Function?
Which cancers?

Answer 28

• Control of the cell cycle and apoptosis

- Breast cancers and several others

Question 29

APC gene;

Function?
Which cancer?

Answer 29

• Control of the cell cycle and apoptosis and differentiation
• Colon cancer

Question 30

Mutations in nucleotide excision repair genes can cause which cancers?

Answer 30

Skin cancers

Question 31

Mutations in mismatch repair genes can cause which cancer?

Answer 31

Colon cancer

Question 32

Mutations in BRCA1 and BRCA2 can cause which cancer?

Answer 32

Breast and ovarian cancer

Question 33

How can viruses in rodents and chickens cause cancer? (2)

Answer 33

• Recruit and modify versions of proto-oncogenes and activate them
• Activate them by inserting powerful viral enhancers sequences next to them

Question 34

How is cervical cancer caused?

Answer 34

• Caused by the human papillomavirus
• Encodes proteins E6 & E7
• These inactivate key tumour suppressor genes
  (RB1 & TP53)