Genes and Cancer

Question 1

What is metastasis?

Answer 1

When cancerous cells enter blood vessels or lymphatics and spread to different sites around the body

Question 2

What is carcinogenesis? What is it driven by?

Answer 2

The process of cancer formation. Driven by mutations and in some somatic tissues epigenetic changes

Question 3

What is hyperplasia?

Answer 3

Cell dividing more rapidly than usual - it is not cancer, it can be a normal response to certain stimuli

Question 4

What is dysplasia?

Answer 4

Cells change form - it is not cancer, can be a normal response to certain stimuli

Question 5

What is meant by ‘tumours are monoclonal’?

Answer 5

All the tumour cells descend from a single starting cell (does not mean all tumour cells are identical!)

Question 6

What are the two types of mutations that arise in tumour cells?

Answer 6

Driver gene mutations

Passenger mutations

Question 7

Define passenger mutation

Answer 7

Mutation with no direct or indirect effect on selective growth advantage of the cell in which it occurred

Question 8

Define driver gene mutation

Answer 8

Mutation that directly or indirectly confers a selective growth advantage to the cell in which it occurs

Question 9

What is the general ratio of driver:passenger mutations an adult tumour may have?

Answer 9

5-8 : hundreds
Driver:Passenger

Question 10

Where are the three main checkpoints in the cell cycle?

What do they check?

Answer 10

Restriction point (start transition, before moving out of G0): Is environment favourable for division?

G2/M transition: Is all DNA replicated? Is environment favourable for division?

Metaphase to anaphase transition: Are all chromosomes properly attached to the spindle?

Question 11

What is the M-Cdk?

Answer 11

Cyclin B with Cdk1

Question 12

What id the S-Cdk?

Answer 12

Cyclin A with Cdk2

Question 13

What is the G1/S-Cdk?

Answer 13

Cyclin E with Cdk2

Question 14

What is the G1-Cdk?

Answer 14

Cyclin D with Cdk 4 and/or Cdk 6

Question 15

Which Cdk does cyclin B bind with?

Answer 15

Cdk1

Question 16

Which Cdk does cyclin A bind with?

Answer 16

Cdk2

Question 17

Which Cdk does cyclin E bind with?

Answer 17

Cdk2

Question 18

Which Cdk does cyclin D bind with?

Answer 18

Cdk4 and Cdk6

Question 19

What are the main cyclins involved in the cell cycle? Which stages do they control?

Answer 19

Cyclin D [G1]
Cyclin E [G1/S transition]
Cyclin A [S]
Cyclin B [Mitosis]

Question 20

What type of residues do Cdks have?

Answer 20

Serine / threonine kinases

Question 21

What activates a Cdk’s kinase activity?

Answer 21

Being bound to its cyclin

Question 22

Describe Cdk protein levels throughout the cell cycle

Answer 22

Protein levels are relatively constant throughout cell cycle. Their activities rise and fall governed by cyclin interactions

Question 23

Gene encoding EGFR is mutated in what percentage of brain tumours, breast cancers and ovarian cancers?

Answer 23

40-50% brain tumours
20% breast cancers
15-30% ovarian cancers

Question 24

CCND1 gene (encodes cyclin D) is mutated in what percentage of oesophageal carcinomas, bladder cancers, and breast cancers??

Answer 24

CCND1 gene is amplified in 35% of oesophageal carcinomas, 15% of bladder cancers and 15% breast cancers

Question 25

What age group does retinablastoma affect?

Answer 25

Children from birth to 4 years

Question 26

How is retinablastoma screened for in the UK?

Answer 26

White light shone in eye.
Reflection from normal retina appears red.
White reflection may indicate retinablastoma.

Question 27

What percentage of children worldwide with retinablastoma die?

Answer 27

87%

Almost exclusively in countries lacking robust screening systems

Question 28

What is retinablastoma? (disease)

Answer 28

Most common eye tumour in children, affecting 1/20000 children. Arises in immature rapidly dividing retinal cells.

Question 29

What percentage of cases of retinablastoma are sporadic with no family history? How does it present?

Answer 29

60% of cases are sporadic, unilateral single tumours in one eye

Question 30

What percentage of cases of retinablastoma are hereditary? How does it present?

Answer 30

40% of cases are hereditary, with multiple tumours, bilateral in both eyes

Disease appears dominant (though actual allele is recessive, its HIGHLY likely to get it because every cell only needs one allele to mutate now to become homozygous recessive [LOH])