Cancer (L18)

Question 1

What is a germline mutation?

Answer 1

A mutation in a cell that goes on to make gametes, passed on to next generation

Question 2

What is a somatic mutation, and what can it lead to?

Answer 2

Mutation in in other cells (not gametes), cannot be passed on, lead to cancer

Question 3

What signals to cancer cells no longer respond (well) to?

Answer 3

many of the signals that control cellular growth and death

Question 4

What is metastasis? When does it occur?

Answer 4

In late stages, cells break through normal tissue boundaries and metastasise (spread) to new sites in the body

Question 5

The more times a cell divides, the more likely it is to…

Answer 5

develop a mutation

Question 6

The likelihood of mutation increases with the number of times a cell has…

Answer 6

divided

Question 7

Why does cancer risk increase with age?

Answer 7

Cancer is the result of an accumulation of mutations, hence why risk of cancer increases with age

Question 8

What causes mutations?

Answer 8

Mutations may be spontaneous (occur by chance) or the result of exposure to a mutagen (also called carcinogen)

Question 9

What do tumour suppressor genes normally encode?

Answer 9

proteins that normally prevent uncontrolled cell growth e.g.
○ proteins that inhibit cell division
○ prevent other mutations (= DNA repair enzymes)

Question 10

What happens when tumour suppressor genes are down regulated?

Answer 10

cell growth i.e. recessive mutation -> cancer

Question 11

What is the process of sending a signal for cell division?

Answer 11

(external) signal for transcription -> unbinding of tumour suppressor genes -> release of transcription factor -> nucleus -> cell division genes expressed

Question 12

What type mutation in tumour suppressor genes usually leads to cancer?

Answer 12

loss of function mutation

Question 13

What is an onco-gene?

Answer 13

A gene which encodes proteins that promote cell growth e.g. proteins that stimulate cell division
Normal function = to produce cell growth

Question 14

What type of mutation in an onco-gene typically leads to cancer?

Answer 14

Dominant mutations (gain of function)

Question 15

What happens if we are missing a tf that represses transcription?

Answer 15

Loss of regulation = expressed at wrong time/place = more growth-stimulating protein = more cell division (at wrong time/place)

Question 16

What happens if there is a mutation in the region of the gene which encodes regulation? (rather than in transcripted region effecting folding)

Answer 16

Proteins have sequence where recognised by protease. If mutation here, protein isn’t recognised by protease so isn’t degraded in response to signal ending cell division = proteins for cell division expressed for longer/active all the time

Question 17

What are the 3 ways that an onco gene leads to increased cell growth?

Answer 17

1. By loss of regulation (e.g. missing the tf that represses transcription) leading to more growth-stimulating protein
2. Mutation in regulatory region of gene, leading to protein always active or not degraded (expressed for longer)
3. Gene duplication - accidental over-replication may lead to expression in other parts of the cell = protein made/expressed too much

Question 18

Describe ‘leukemia’

Answer 18

A group of blood cancers resulting in high numbers of abnormal cells (not fully developed blood cells called blasts/leukaemia cells)

Question 19

What is a clinical condition/example of how oncogene and tumour suppressor mutations lead to cancer?

Answer 19

Chronic Myeloid Leukaemia

Question 20

Describe the mutation that causes Chronic Myeloid Leukaemia

Answer 20

• Translocation leading to oncogene BRC-ABL (chromosome 9 and 22
  = new gene that is a little of BRC gene and mostly ABL gene so under the wrong regulatory sequence = too much of weird protein all the time

Question 21

How is the ABL protein normally turned on?

Answer 21

ABL protein normally needs cell signal to be activated and produce tf that turns on cell division

Question 22

What happen to ABL activation with mutation?

Answer 22

With translocation, always on, can always activate tf, doesn’t need cell signal

Question 23

Why doesn’t one wrong thing or one mutation necessarily lead to cancer

Answer 23

Because multiple transcription factors are needed to control replication of a gene and .: cell replication/division

Question 24

So what 3 things need to happen to make cancerous cells?

Answer 24

1x oncogene = accelerator
○ DOMINANT mutation = gain of function = growth signals = uncontrolled growth

2x loss of function mutations in the same tumour suppressor gene
○ RECESSIVE mutation = loss of function predisposes you to cancer

Question 25

What are possible treatments for cancer?

Answer 25

• Surgery to remove cells
  ○ Especially if early on
• Radiation therapy
  ○ Targeted to tumour
• Chemotherapy
  ○ Chemicals that result in less components for DNA replication = inhibits cell replication