Epigenetics and Cancer. Oncogenes and Tumour Suppressor Genes
Laura Armstrong
Teacher
Contents
Recall Questions
This topic requires prior knowledge of epigenetics from year 13 and cancer from year 12. You can test your knowledge below.
What is epigenetics?
The study of heritable changes in gene expression that do not involve changes to the DNA base sequence.
What is DNA methylation and what does it do to gene expression?
It is the addition of a methyl group to DNA; it typically switches off gene expression by preventing transcription.
What is a tumour?
A mass of abnormal cells.
What genes regulate the cell cycle?
Tumour suppressor genes and proto-oncogenes.
Topic Explainer Video
Check out this @LauraDoesBiology video that explains epigenetics and cancer. benign and malignant tumours. oncogenes and tumour supressor genes or read the full notes below. Once you've gone through the whole note, try out the practice questions!
How Can Epigenetic Changes Lead to Cancer?
Cancer is caused by uncontrolled cell division, often due to mutations or abnormal gene expression of key regulatory genes:
- Tumour suppressor genes (TSGs).
- Proto-oncogenes.
Epigenetic modifications — especially methylation and acetylation — can affect how these genes are expressed without altering the DNA sequence.
Cancer Risk from Changes to Methylation
1. Tumour Suppressor Genes (TSGs)
Normal function:
- TSGs code for proteins that prevent uncontrolled cell division.
- They repair damaged DNA, trigger apoptosis (cell death), or pause the cell cycle.
Epigenetic change: Hypermethylation
- Increased methylation of promoter regions of TSGs.
- Transcription is inhibited, so the TSG is not expressed.
- The tumour suppressor protein is not produced
- As a result, cell division is unregulated → uncontrollable cell division → tumour formation.
Example: Hypermethylation of the BRCA1 gene (a TSG) is linked to breast cancer.
2. Proto-oncogenes
Normal function:
-
Proto-oncogenes code for proteins that stimulate normal, controlled cell division when needed (e.g. in growth or repair).
Epigenetic change: Hypomethylation
- Decreased methylation = proto-oncogenes become overactive.
- They are transcribed too much, even when not needed.
- This leads to uncontrollable cell division → tumour formation.
When a proto-oncogene becomes overactive, it’s called an oncogene.
Summary: Methylation and Cancer
| Gene Type | Epigenetic Change | Effect on Gene Expression | Resulting Risk |
| Tumour Suppressor Gene | Hypermethylation | Gene expression switched off | Uncontrolled cell division (loss of control) |
| Proto-oncogene | Hypomethylation | Gene expression switched on | Excessive cell division (too active) |
Cancer Risk from Changes to Acetylation
How Acetylation Affects Gene Expression
- Acetylation = addition of an acetyl group (–COCH₃) to histone proteins.
- This reduces the positive charge on histones, weakening their attraction to DNA.
- DNA becomes loosely coiled making genes more accessible to transcription factors → increased transcription and increased gene expression.
1. Decreased Acetylation
- Leads to tight packing of DNA around histones.
- Transcription factors and RNA polymerase cannot access genes → no transcription (gene is silenced).
- If this happens to a tumour suppressor gene, it is switched off, allowing uncontrolled cell division.
2. Increased Acetylation
- In some cases, excessive acetylation may overactivate proto-oncogenes.
- This could lead to their constant expression, even when cell division is not needed.
- This turns proto-oncogenes into oncogenes, promoting excessive and unregulated cell division.
Summary: Acetylation & Cancer
| Gene Type | Epigenetic Change | Effect on Gene | Resulting Risk |
| Tumour suppressor gene | ↓ Acetylation. | Gene expression switched off. | No control of cell division or apoptosis. |
| Proto-oncogenes | ↑ Acetylation. | Gene overexpressed. | Excessive cell division. |
Key Terms
- Tumour Suppressor Gene: Gene that normally stops cell division or causes apoptosis.
- Proto-oncogene: Gene that normally promotes cell division in a regulated way.
- Oncogene: A mutated or overexpressed proto-oncogene that causes uncontrolled cell division.
- Hypermethylation: Excessive addition of methyl groups to DNA, leading to gene silencing.
- Hypomethylation: Removal or absence of methyl groups, leading to gene overexpression.
No answer provided.
Exam Tip
When asked about epigenetics and cancer:
- Always name the specific gene type (TSG or proto-oncogene).
- Explain how epigenetic changes affect gene expression and how it contributes to cancer (i.e. uncontrolled cell division).
No answer provided.
MDS (a group of malignant cancers) can develop from epigenetic changes to tumour suppressor genes. In some patients, the drug AZA has reduced the effects of MDS. AZA is an inhibitor of DNA methyltransferases. These enzymes add methyl groups to cytosine bases.
Suggest and explain how AZA can reduce the effects of MDS in some patients. (3 marks)
1. AZA reduces methylation of DNA / cytosine / gene
2. Tumour suppressor gene is transcribed / expressed
3. Prevents rapid / uncontrollable cell division
OR
Cell division can be controlled / stopped / slowed
Practice Question
Try to answer the practice question from the TikTok on your own, then watch the video to see how well you did!