Lecture 2: Oncogenes and Tumour Suppresors

Question 1

What is carcinogenesis a consequence of?

Answer 1

• gain of function of oncogenes (GO; uncontrolled proliferation)
• loss of function of tumour suppresor genes (STOP, which normally act to constrain cell proliferation)

Question 2

What are the mechanisms of oncogenic activation?

Answer 2

Oncogenes are activated as a result of DNA mutations:
- Point mutations: can result in a single amino acid substitution leading to constitutive activation or increased protein stability
- Truncations: Loss of a portion of a protein can result in the loss of an important regulatory domain
- Translocations:
i) Genes can be translocated to a genome location with high transcriptional rates
ii) Genes can be translocated to other gene locus resulting in a chimeric dysfunctional protein
- Gene amplification: increases the number of gene copies
- Chromosomal gain: The acquisition of an additional chromosome containing oncogenes (i.e. Chr8)

Question 3

What is an example of a single point mutation in an oncogene?

Answer 3

Ras activation by a single-point mutation at codon 12