Cancer Genomes

Question 1

State a cause of cancer.

Answer 1

Genetic. Epigenetic mutations. Environmentally induced cancer.

Question 2

How does cancer develop?

Answer 2

Clonal expansion.

Question 3

State a feature of constitutional mutations.

Answer 3

Chromosomal imbalance. Single gene disorder - tumour suppressors, oncogenes. Imprinting abnormality.

Question 4

State a feature of somatic mutations.

Answer 4

Cannot be inherited - occur in non-germline tissues.

Question 5

State a feature of germ-line mutations.

Answer 5

Can be inherited - present in egg or sperm.

Question 6

State a difference between driver mutation and passenger mutation.

Answer 6

Driver mutation - implicated in oncogenesis and have growth advantage. Passenger mutation - not been selected for, not conferred a clonal growth advantage (not contribute to cancer).

Question 7

Give 1 example of a oncogene.

Answer 7

Her2-neu - breast. Ras. Myc. Src. Htert. Kras - colorectal. BRAF - melanoma.

Question 8

Give 1 example of a tumour suppressor gene.

Answer 8

p53. Rb. APC. BRCA1. BRCA2.

Question 9

Give an example of a DNA repair gene.

Answer 9

BRCA1. BRCA2.

Question 10

State a cause of oncogene activation.

Answer 10

Chromosomal translocation. Gene amplification. Intragenic mutation.

Question 11

How do tumour suppressor gene mutations contribute to cancer development?

Answer 11

Mutations inactivate inhibitory functions.

Question 12

What is Knudson’s two-hit hypothesis?

Answer 12

Non-hereditary individual - requires a 2 hit ‘event’ (mutate both chromosomes) for a tumour. Hereditary individual - 1 hit event for a tumour.

Question 13

State one way a hereditary mutation differ to a non-hereditary mutation?

Answer 13

Individuals with genetic mutation - more likely to develop tumour, more likely to develop tumour at a younger age.

Question 14

What is a retinoblastoma?

Answer 14

Cancer in retina affecting young children.

Question 15

What is a phaeochromocytoma?

Answer 15

Tumour of the adrenal gland - increases adrenaline (hormone controlling the heart rate/metabolism/BP).

Question 16

What is lynch syndrome?

Answer 16

Hereditary non-polyposis colorectal cancer - associated with predisposition to different cancers e.g. ovarian cancer, stomach, breast, liver, kidney.

Question 17

What is meant by medullary thyroid cancer?

Answer 17

Originates from parafollicular cells which produce calcitonin.

Question 18

State 3 hallmarks of cancer.

Answer 18

Sustaining proliferative signalling. Evading growth suppressors. Activating invasion and metastasis. Enabling replicative immortality. Resisting cell death. Avoiding immune destruction. Tumour-promoting inflammation. Genome instability and mutation. Deregulating cellular energetics.

Question 19

State a platinum based chemotherapy used to treat breast cancer.

Answer 19

Carboplatin - ensures DNA-cross links (DNA repair), prevent broken, damaged DNA from accumulating to cause cell death.

Question 20

State an example of a PARP inhibitor.

Answer 20

Olaparib (in ovarian cancer) - ensures single-strand DNA breaks which are converted to double stranded DNA. This can be lethal for BRCA-deficient cells.

Question 21

State a characteristic of Lynch syndrome.

Answer 21

Microsatellites (STRs) - have PD-L1 receptor which deactivates T cells to produce an immunosuppressive environment.

Question 22

What does pembrolizumab do?

Answer 22

Ensures PD1-inhibition - create an immunosuppressive environment.

Question 23

What does EGFR stand for, and what is its role in lung cancer?

Answer 23

Epidermal Growth Factor Receptor. Over expressed in non-small cell lung cancer - acts as an oncogene to promote cancer.

Question 24

State a tyrosine kinase inhibitor.

Answer 24

Gefitinib. Erlotinib.

Question 25

State the function fo a tyrosine kinase inhibitor.

Answer 25

Blocks the pathway - prevents lung cancer.

Question 26

What is the difference between somatic and constitutional mutations?

Answer 26

Somatic - present in the tumour only. Constitutional - present in tumour and all other cells in the body.