Lecture 4: Cancer 1

Question 1

What is cancer?

Answer 1

A group of diseases generally characterised by genomic instability and uncontrolled cell division and leading to invasion of surrounding tissue and eventual dispersion to distant sites.

Question 2

Which cancers are the 4 main killers?

Answer 2

• large bowel
• breast
• prostate
• lung (smoking)

Question 3

How many different cancers are there?

Answer 3

Over 200. You can get cancer in any cell type in your body, e.g. bone cancer

Question 4

How might the karyotype from a cancer tissue differ to one from a healthy tissue/person?

Answer 4

The karyotype of the cancer-ridden tissue will have multiple/too many chromosomes or missing chromosomes.

Question 5

What is a PAP test?

Answer 5

A cervical smear stain for proliferating cells. It is stained for proteins important in S phase (e.g. cdm6, mcm5), which indicate dividing cells, showing cervical cancer by turnover. This is much simpler than other testing methods and doesn’t require the tester to be highly trained.

Question 6

How can a tumour form in an epithelial layer?

Answer 6

An epithelial layer is full of cells so there is no space for cells to divide into. The cells are constantly sending messages to the surrounding cells telling them not to divide. A cancer-causing cell will ignore these messages and divide anyway, causing a tumour to develop in the epithelial layer. Tumours grow in any space available to it and invade other tissues. This is way they can cause a bump.

Question 7

What is metastasis?

Answer 7

When cancer cells escape their original position, via the circulatory system (bloodstream) and invades other tissues. This leads to tumours all over the body and is very difficult to treat. The cancer cells will accumulate in organs with a good blood supply, such as the lungs or liver. Most cancer cells won’t undergo metastasis, but some will.

Question 8

Why do cells undergo metastasis?

Answer 8

When the cancer cell is in a tumour with many other cancer cells there is lots of competition between the cancer cells for nutrients, etc.
Cancer cells have an unstable genome, which allows them to evolve quickly to suit a niche. This means that if a cancer cell undergoes metastasis, it can find a new niche where there is no competition from other cancer cells, so the cancer cell can grow quickly there.
Cancer cells are motile, so they can move to find better conditions or more space to divide.

Question 9

Why is it especially bad when an organ is riddled with many tiny tumours?

Answer 9

This can lead to organ failure and is very difficult to treat as the tumours are too tiny and numerous to be removed.

Question 10

What is angiogenesis?

Answer 10

The generation of new blood vessels. Tumours can induce angiogenesis by secreting factors. The new chaotic (don’t need to be ordered) blood vessels supply the tumour with oxygen and nutrients and gives the tumour an escape route.

Question 11

What are the differences between benign and malignant tumours?

Answer 11

Benign tumours have some cell proliferation, but it is contained within a small area and is not very sustained. There is insufficient genetic change to be a malignant tumour. However, benign tumours can become malignant tumours over time, so they are often removed just in case.

Malignant tumours are often the same size as benign tumours, but have more prolonged proliferation and have more cells in S phase. Malignant tumours are better at undergoing metastasis.

Question 12

Give descriptions of 4 common types of tumour.

Answer 12

• carcinoma = epithelial cell derived (accounts for more than 85% of all cancers)
• lymphoma = cancer of lymphocytes
• leukaemia = white blood cell derived - leukocyte
• sarcoma = cancer of connective tissue or bone

Question 13

What are the 3 main causes of cancer?

Answer 13

• Inheritance (e.g. selective breeding of poodles for cuteness has selected cancer genes too)
• Genetic change: Mutagens, irradiation, chemicals (largely responsible for most human cancers)
• Viral infection

Question 14

How many breast cancer cases have a family history of cancer?

Answer 14

10%.

90% of breast cancer cases are sporadic (no family history or link to specific mutation in genome).

Question 15

Give 4 types of mutation which constitute genetic change.

Answer 15

• Point mutation (single nucleotide change)
• Deletion
• Translocation
• Inversion

Question 16

How can point mutations occur?

Answer 16

The deamination of cytosine to uracil happens spontaneously in water all the time. That means that when that DNA is replicated, instead of a C-G pair, a U-A pair is made. The DNA will repair itself and replace the RNA base U with the equivalent DNA base, T.

Question 17

What does aneuploid mean?

Answer 17

It means there is a non-normal number of genome copies (not normal diploid). There may be polyploidy, deletions or translocations. New chromosomes have been created and these have new/different functions.

Question 18

How are cancer and age linked?

Answer 18

Older people are more likely to develop cancer, because their DNA has accumulated mutations over time. Most people over 65 have the beginnings of colon cancer. However, colon cancer is a slow killer, taking 30 to 40 years to kill, so most people die or something else before the colon cancer can kill them.

Question 19

What are mutations to the BRCA1 and BRCA2 genes associated with?

Answer 19

Mutations in the BRCA1 and BRCA2 genes increase the susceptibility to breast cancer from 2% to 5-50% and increases the chances of cervical cancer slightly.
The BRCA1 and BRCA2 genes are involved in DNA repair,

Question 20

What is the danger of genetic testing for mutated genes?

Answer 20

A positive test doesn’t mean it is certain that that person will develop cancer, but it can be misinterpreted by the public very easily.

Question 21

What is cellular homeostasis?

Answer 21

A founder cell has a mutation which gives it an advantage over its neighbouring cells for dividing earlier or quicker. This fast division means that it picks up other mutations faster than the neighbouring cells. These mutations could help the cell divide/survive in other conditions.

Question 22

How are cancer cells affected by Darwinian selection?

Answer 22

All of the cancer cells are competing against each other. The cell with the best mutations for forming a tumour is selected for. This means that the tumours is made up of one strong cell type.

If a drug is discovered which targets one mutation, the cells with that mutation are no longer selected as the best for forming tumours, so other cells with different mutations are selected for. This means that other tumours are made, which are resistant to the original drug. To try to combat this effect, cancer patients are given a cocktail of different drugs in chemotherapy.

Question 23

Why is it so very difficult to treat cancer?

Answer 23

• There are over 200 different types of cancer
• For any given type of cancer, the genetic changes can be very variable. Cells don’t always have the same combination of mutated genes for the same cancer.
• There are over 30,000 changes between normal and malignant colon and we don’t know all of the changes.
• Cancer cells are affected by Darwinian selection so become resistant to drug treatment over time.