3rd Feb - Aneuploidy, CIN and Mitotic errors Flashcards

1
Q

What is aneuploidy?

A

The presence of an abnormal number of chromosomes in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How can aneuploidy be detected?

A

By FISH on the whole karyotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the most common genetic change associated with cancer?

A

Aneuploidy present in >90% of cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give an example of a common aneuploidy in cancer

A

Chr 3 in melanomas

Chr 7 in renal carcinomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is CIN?

A

Chromosome instability - a type of genomic instability in which chromosomes are unstable such that whole or parts of chromosomes are duplicated/deleted, over generations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does CIN cause?

A

Different cells within the tumour have quite different sets of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the two different forms of CIN?

A

Numerical

Structural

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What causes numerical CIN?

A

Results from errors in chromosome segregation during mitosis such as:

  • Defective chromosome cohesion
  • Centrosome amplification
  • Merotelic chromosome attachments
  • Mitotic checkpoint defects
  • Cell division failure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What causes structural CIN?

A

Could result from mitotic errors or pre-mitotic errors such as replication stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are sister chromatids held together?

A

They must be held together from S phase to anaphase
They are held together by cohesion complexes: SCC1, SCC3, SMC1 and SMC3 which form a ring around the sister chromatids. They are loaded onto chromsomes at the beginning of the cell cycle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Outline common mutations causing loss of sister chromatid cohesion

A

Mutations in cohesin are common in colorectal cancer

Inactivating mutations in SCC3 cause premature loss of cohesion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do cancer cells acquire multiple centrosomes?

A

Uncoupling of centrosome duplication from the cell cycle

Failure of cells to divide during mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How have cancer cells adapted to prevent cell death from chromosome missegregation caused by centrosome amplification?

A

Centrosome clustering causes multiple centrosomes to cluster creating pseudo-bipolar mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Outline the process of kinetochore attachment in a functional cell

A
  1. Unattached chromosome at pro-metaphase
  2. 1 kinetochore binds laterally to a control MT
  3. Chromosome slides towards the spindle pole
  4. Lateral attachment inverts to an end-on unipolar attachment, microtubule now called kinetochore MT
  5. Free kinetochore captures microtubules from opposite spindle pole to convert unipolar to bipolar attachment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is a syntelic chromosome attachment?

A

Some centrosomes attach to kinetochores on both sister chromatids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is merotelic chromosome attachment?

A

Both centrosomes have spindles which attach to the same kinetochore

17
Q

What is amphitelic chromome attachment?

A

Normal attachment

18
Q

When was aneuploidy first associated with tumours?

A

In 1890 by David Homemann and Theoder Boresi

19
Q

What is mosaic variegated aneuploidy?

A

Mutations in the BubR1 gene which causes growth retardation, microcephaly, childhood cancer and often results in early death due to premature sister chromatid seperation in >50% of lymphocytes