Chromosomes and Cancer

Question 1

What is molecular cytogenetics?

Answer 1

Comparison of normal and cancer cells based on contents of chromosomes

Question 2

What kind of chromosome abnormalities occur in neoplastic cells?

Answer 2

• Changes to structure of individual chromosome
• Changes in chromosome number

Question 3

What is a clastogen?

Answer 3

A substance which causes disruption of chromosomes

Question 4

What are the 3 categories of chromosomal abnormality?

Answer 4

• Primary abnormality
• secondary abnormality
• Cytogenic noise

Question 5

What are primary chromosomal abnormalities?

Answer 5

• Involved in establishing tumour
• Genes whose normal mutations relieves normal controls on cell division, death or lifespan

Question 6

What are secondary chromosomal abnormalities?

Answer 6

• Occur after tumour development and may be important in tumour progression
• Disruption causes genome instability and increases frequency of alterations in gatekeeper genes

Question 7

What us cytogenic noise?

Answer 7

Background level of non-consequential aberrations

Question 8

Give some mechanisms for oncogene activation

Answer 8

• Point mutation in DNA sequence
• Overexpression of normal protein
• Chromosome translocations or rearrangments giving new gene products or move protooncogenes onto transcriptionally active region

Question 9

What are double minutes?

Answer 9

Small fragments of extra-chromosomal DNA observed in a large number of tumours

Question 10

What do double minutes look like in karotype?

Answer 10

Pairs of dots around chromosomes

Question 11

What kind of genes do double minutes usually contain?

Answer 11

Amplified oncognes and genes involved in drug resistance

Question 12

What are the features of common chromosomal defects in solid tumours?

Answer 12

• Numerous rearrangments with groos aneuploidy

Question 13

What are the features of typical chromosomal defects in haemotopoetic tumours?

Answer 13

• Usually have rearrangments involving only a few abnormal chromosomes
• Otherwise normal diploid karyotype

Question 14

What translocation occurs in Burkitt’s lymphoma?

Answer 14

c-myc is located to an antibody loci and causes overexpression

Question 15

What translocations are typical of follicular lymphoma?

Answer 15

• entire coding sequence of bcL-1 is translocated
• Leads to unregulated high levels of Bcl-2 protein

Question 16

How does Bcl-2 overexpression support cancer cells?

Answer 16

Protects cells against apoptosis, increases survival rather than cell proliferation

Question 17

What chromosome translocation is often found in chronic myeloid leukaemia?

Answer 17

A philadelphia chromosome

Question 18

How does a philadelphia chromosome support cancer?

Answer 18

• Creates bcr-abl gene
• Produces increased TK activity which can drive cell cycle in cancer cells

Question 19

What is chromothripsis?

Answer 19

Mutational process where thousands of clustered chromosomal rearrangments occur in a single event

Question 20

What is the usual cause of changes in chromosome number?

Answer 20

Mis-segregation of chromosomes during mitosis

Question 21

What usually monitors correct spindle assembly?

Answer 21

Spindle assembly checkpoint

Question 22

Give some examples of genetic instability syndromes

Answer 22

• Bloom’s syndrome
• Fanconi’s anaemia

Question 23

What happens in Bloom’s syndrome?

Answer 23

50% of patients have one cancer by age of 25