Chromosomes and Cancer Flashcards
What is molecular cytogenetics?
Comparison of normal and cancer cells based on contents of chromosomes
What kind of chromosome abnormalities occur in neoplastic cells?
- Changes to structure of individual chromosome
- Changes in chromosome number
What is a clastogen?
A substance which causes disruption of chromosomes
What are the 3 categories of chromosomal abnormality?
- Primary abnormality
- secondary abnormality
- Cytogenic noise
What are primary chromosomal abnormalities?
- Involved in establishing tumour
- Genes whose normal mutations relieves normal controls on cell division, death or lifespan
What are secondary chromosomal abnormalities?
- Occur after tumour development and may be important in tumour progression
- Disruption causes genome instability and increases frequency of alterations in gatekeeper genes
What us cytogenic noise?
Background level of non-consequential aberrations
Give some mechanisms for oncogene activation
- Point mutation in DNA sequence
- Overexpression of normal protein
- Chromosome translocations or rearrangments giving new gene products or move protooncogenes onto transcriptionally active region
What are double minutes?
Small fragments of extra-chromosomal DNA observed in a large number of tumours
What do double minutes look like in karotype?
Pairs of dots around chromosomes
What kind of genes do double minutes usually contain?
Amplified oncognes and genes involved in drug resistance
What are the features of common chromosomal defects in solid tumours?
- Numerous rearrangments with groos aneuploidy
What are the features of typical chromosomal defects in haemotopoetic tumours?
- Usually have rearrangments involving only a few abnormal chromosomes
- Otherwise normal diploid karyotype
What translocation occurs in Burkitt’s lymphoma?
c-myc is located to an antibody loci and causes overexpression
What translocations are typical of follicular lymphoma?
- entire coding sequence of bcL-1 is translocated
- Leads to unregulated high levels of Bcl-2 protein
How does Bcl-2 overexpression support cancer cells?
Protects cells against apoptosis, increases survival rather than cell proliferation
What chromosome translocation is often found in chronic myeloid leukaemia?
A philadelphia chromosome
How does a philadelphia chromosome support cancer?
- Creates bcr-abl gene
- Produces increased TK activity which can drive cell cycle in cancer cells
What is chromothripsis?
Mutational process where thousands of clustered chromosomal rearrangments occur in a single event
What is the usual cause of changes in chromosome number?
Mis-segregation of chromosomes during mitosis
What usually monitors correct spindle assembly?
Spindle assembly checkpoint
Give some examples of genetic instability syndromes
- Bloom’s syndrome
- Fanconi’s anaemia
What happens in Bloom’s syndrome?
50% of patients have one cancer by age of 25
