Cancer-critical Genes preclass 23

Tumor suppressors 1

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 2

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

Tumor suppressors 2.1 caused by

Loss of function mutations

1. Lower expression levels

2. Changes that destabilize the protein

3. Mis-localization of the protein

4. Loss of an activation site 

Tumor suppressors 2.2 caused by

Caused by

1. Nucleotide substitutions

2. Insertions/deletions (indels) that cause early stop codons

3. Changes that inactivate regulatory sequences like promoters or enhancers

4. Epigenetic changes that silence a gene

Oncogenes 1

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 2

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

Oncogenes 2.1

Gain-of-function mutations

1. Increase expression

2. increased stabilization 

3. Constitutively active/ unregulated activity

4. Constitutive localization

Oncogenes 2.1 caused by

Caused by

1. Nucleotide substitutions

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

3. Changes in regulatory sequences like promoters and enhancers that increase transcription

4. Epigenetic changes that open the chromatin around a gene

Cancers often have

mutations in both types of genes