Cancer-critical Genes Tumor suppressors and Oncogenes

Tumor suppressors

Tumor suppressors are genes whose wild-type function is to prevent

development of tumors and cancer

1. Block cell division

2. Induce apoptosis

3. Reduce DNA damage

4. Respond to anti-proliferation signals

5. Increase connectedness to original tissue location

And others

Mutations that inactivate tumor suppressors contribute to cancer

Tumor suppressors

Loss of function mutations

- Lower expression levels

- Changes that destabilize the protein

- Mis-localization of the protein

- Loss of an activation site

Caused by

- Nucleotide substitutions

- Insertions/deletions (indels) that cause early stop codons

- Changes that inactivate regulatory sequences like promoters or enhancers

- Epigenetic changes that silence a gene

Oncogenes

Oncogenes are genes whose wild-type function favors tumor or cancer

development

1. Promote cell division

2. Block apoptosis

3. Increase cell detachment

4. Increase cell mobility

5. Block DNA repair

Wild-type version is called a proto-oncogene

Hyperactive version is called an oncogene

Oncogenes

Gain-of-function mutations

- Increase expression

- Increased stabilization

- Constitutively active/ unregulated activity

- Constitutive localization

Caused by

- Nucleotide substitutions

- Rarely by insertions/deletions (indels) that cause early stop codons

- Changes in regulatory sequences like promoters and enhancers that

increase transcription

- Epigenetic changes that open the chromatin around a gene