Cancer

Question 1

What is the definition of cancer?

Answer 1

Uncontrolled cell growth

Question 2

What are the main environmental risk factors?

Answer 2

Sunlight - UV light
Radiation
Chemical
Viruses

Question 3

What are the main lifestyle risk factors?

Answer 3

Diet
Smoking
Exercise

Question 4

What is the biggest risk factor?

Answer 4

Age

Question 5

What is chromothripsis?

Answer 5

‘Chromosome shattering’

High numbers of rearrangements in localised region

Question 6

What is DNA stress?

Answer 6

Inefficient replication that leads to the replication fork slowing, stalling and / or breakage

Question 7

When does DNA stress arise?

Answer 7

Increase in causes of replication fork defects

Defects in processing / response pathways

Question 8

What do proto-oncogenes do?

Answer 8

Regulate various aspects of cell growth and division

Question 9

How are tumour suppressor genes characterised?

Answer 9

Gatekeepers: regulate cell proliferation
Caretakers: act to prevent genomic instability

Question 10

What is the DNA damage response?

Answer 10

Signalling pathways that act to prevent genomically unstable cells from continuing to proliferate

Question 11

What is senescence?

Answer 11

Permanent cell cycle arrest

Question 12

What are the main repair pathways?

Answer 12

Base-excision repair
Nucleotide-excision repair
Recombinational repair
Mismatch repair

Question 13

How does non homologous end joining work?

Answer 13

KU70/80 protects double strand break ends
DNA-PKcs - process ends if required to remove damaged DNA components
Ligation of two broken ends back together

Question 14

How does homology-directed repair work?

Answer 14

Uses homologous template (sister chromatin preferably)

Occurs in S and G2/M phase

Question 15

What happens to the DNA damage response in cancerous cells?

Answer 15

It’s switched off. Permits growth despite high DNA damage and genomic instability levels

Question 16

What are the functions of BRCA1?

Answer 16

Double strand break repair
DNA replication stress response
Chromatin modification 
Transcription regulation 
Cell cycle checkpoints
Tumour suppressor (caretaker and gatekeeper)

Question 17

What are the functions of BRCA2?

Answer 17

Double strand break repair
DNA replication stress response
Tumour supressor

Question 18

What are the steps of colorectal cancer?

Answer 18

Normal cell -> Hyperpoliferation -> Adenoma -> Carcinoma

Question 19

Mutations in what areas can lead to colorectal cancer?

Answer 19

APC gene mutation
K-ras mutation
DDC gene mutation
P53 mutation

Question 20

How do somatic mutations vary within the same cancer type?

Answer 20

Different cancers are different in many ways - mutation types and genes involved.
Same tumour in different people vary
Pattern of mutation accumulation vary
Inter-tumour heterogeneity

Question 21

How is cancer therapy a paradox?

Answer 21

Inducing DNA damage and replication stress is often a mechanism of cancer cell death during therapy

Question 22

How does personalised therapy work?

Answer 22

Tailor therapies to genotype of patient and . or tumour
Genotype normal tissue for comparison
Genotype after treatment and adjust therapy to combat newly evolved clones