Cancer cell biology

Question 1

What is tumour heterogeneity?

Answer 1

Subpopulations of cells with distinct genotypes and phenotypes, may have divergent biological behaviours
Within a primary tumour and its metasteses

Question 2

What factors enable tumour heterogeneity?

Answer 2

Genomic and epigenomic mechanisms
Tumour microenvironment and metastasis
Clonal evolution

Question 3

What are the genes involved in the onset of cancer and their normal function, and the effect of mutation?

Answer 3

Proto-oncogenes: Promote cell survival or proliferation. Mutated: gain of function > unregulated cell proliferation and survival
Tumour suppressor genes: Inhibit cell survival or proliferation. Mutated > loss of function mutations > unregulated cell proliferation and survival
Genome maintenance gene: repair or prevent DNA damage. Mutated: loss of function > allow mutations to accumulate

Question 4

What forms of protein can result in cancer if mutated?

Answer 4

• Extra and intra-cellular signalling molecules
• Signal receptors
• Signal- transducing proteins
• Transcription factors
• Cell cycle control proteins (function to restrain cell prolif)
• DNA repair proteins
• Apoptotic proteins (TSGs that promote apoptosis, oncoproteins that promote cell survival)

Question 5

What mutational events occur to result in gain vs loss of function of genes?

Answer 5

Overactivity mutation - gain of function
- single mutational event, creates oncogene
- oncogene promotes cell transformation
Underactivity mutation - loss of function
- mutational event 1, inactivates TSG
- no effect of mutation in one gene copy
- mutational event 2, inactivates second gene copy
- two inactivating mutations functionally eliminate the TSG, promoting cell transformation

Question 6

What are the types of activating mutations?

Answer 6

Deletion or point mutation in coding sequence > hyperactive protein in normal amounts
Regulatory mutations > excessive amount of normal proteins
Gene amplification > excessive amount of normal proteins
Chromosome rearrangement > nearby regulatory DNA sequence causes overproduction of normal protein
OR > fusion to actively transcribed gene produces hyperactive fusion protein