Genome and Chromosome Abnormalities in Cancer

Question 1

What is maturation promoting factor?

Answer 1

Cyclin-Cdk complex that stimulates the mitotic and meiotic phases of the cell cycle. It promotes the entrance into mitosis (the M phase) from the G2 phase.

Question 2

What was noticed about cyclin A and B and the cell cycle when they were studied?

Answer 2

They accumulate in interphase and degrade at the end of mitosis.

Question 3

In 1986, Joan Ruderman showed cyclin A triggers…?

Answer 3

G2 to M transition

Question 4

What cyclin-dependent kinase gene is required to pass START?

Answer 4

Cdc28

Question 5

What cyclin-dependent kinase gene is required to arrest cell cycle at G1 and G2 to M transition?

Answer 5

Cdc2

Question 6

What do Cdc28 and Cdc2 both code for?

Answer 6

Cdk1

Question 7

What group of cyclins and cyclin dependent kinases work at G1 to S?

Answer 7

cdk2, cdk4, cdk6 + cyclin D & E

Question 8

What group of cyclins and cyclin dependent kinases work at G0?

Answer 8

cdk4, cdk6 + cyclin D1, D2 & D3

Question 9

What group of cyclins and cyclin dependent kinases work at late G1?

Answer 9

cdk2 + cyclin E1 & E2

Question 10

What group of cyclins and cyclin dependent kinases work through S?

Answer 10

cdk2 + cyclin A1 & A2

Question 11

What group of cyclins and cyclin dependent kinases work at S to G2?

Answer 11

cdk1 + cyclin A1 & A2

Question 12

What group of cyclins and cyclin dependent kinases work at G2 to M?

Answer 12

cdk1 + cyclin B1, B2, & B3

Question 13

What happens where there is a loss of CK inhibitors?

Answer 13

You get hyperactive CDKs, which leads to accumulation of rapidly dividing progenitors and tumour cells.

Question 14

Cyclin D synthesis is induced in response to…?

What happens if this inducer is removed?

Answer 14

Growth factor stimulation

Cyclin D level decreases and this is important as Cdk4, 6/cyclin D complex drive cells through START (G1 to S, and G0).

Question 15

Mutations in continual unregulated expression of cyclin D is associated with…?

Answer 15

Many lymphoma and breast cancers (e.g. mutations that inactive cdk4 and cdk6)

Question 16

What is Rb protein? Inactivation leads to…?

Answer 16

A tumour suppressor (substrate of cdk4/6)

Cancer

Question 17

What inhibits cdk4/6?

Answer 17

p16

Question 18

Cell Cycle/DNA damage checkpoints - what is the point of this?

Answer 18

Prevent entry into next phase of the cell cycle

Question 19

When are the cell cycle checkpoints? (5)

Answer 19

Between G1 and S
In S phase
In G2
Between G2 and M (antephase checkpoint)
In M phase (spindle assembly checkpoint)

Question 20

What are the outcomes of cell cycle arrest? (3)

Answer 20

DNA repair
Cell death
Checkpoint adaptation without DNA repair

Question 21

What are the possible checkpoint adaptations? (2)

Answer 21

Mitotic catastrophe (death after first mitosis)
Genomic and chromosomal abnormalities

Question 22

What are the possible genomic and chromosomal abnormalities? (2)

Answer 22

Chromosomal aberrations - changes in chromosome structure
Genomic aberrations - changes in the number of chromosomes, i.e. addition of all or part of a chromosome (aneuploid), or the gain of one or more complete sets of chromosomes (euploid)

Question 23

Chromosomal abnormalities in cancer can either be chromosomal imbalances or balanced chromosomal rearrangements.
What type of chromosomal imbalances are there? (7)

Answer 23

Genomic gain - e.g. complete trisomy, partial trisomy, intrachromosomal amplification, extrachromosomal amplification
Genomic loss - e.g. monosomy, large scale deletion, submicroscopical deletion

Question 24

Chromosomal abnormalities in cancer can either be chromosomal imbalances or balanced chromosomal rearrangements.
What type of balanced chromosomal rearrangements are there? (2)

Answer 24

Formation of chimeric fusion gene

Deregulated expression of structurally normal gene

Question 25

What is the Philadelphia Chromosome?

Answer 25

Reciprocal translocation between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene codes for a tyrosine kinase signalling protein that is “always on”, causing the cell to divide uncontrollably (causes CML).

Question 26

What euploid aberrations are there? (4)

Answer 26

Cell fusion (2n, 2c x2)
Endoreplication (4n, 4c) - skips M phase
Mitotic slippage (4n, 4c) - doesn't complete M phase
Cytokinesis failure (2n, 2c x2)

Question 27

What are the two potential outcomes of polyploidy? When do they occur?

Answer 27

Arrest/death - if there is an increase of p53

Proliferation (tumour) - loss of p53 or p21, or increased toxins or MYC

Question 28

What aneuploid aberrations are there? (4)

Answer 28

Aberrant mitosis
Cohesion defects
Merotelic centromere attachment
Mitotic checkpoint defects