Cancer genetics

Question 1

What is cancer ?

Answer 1

cells that divide and proliferate uncontrollably due to alterations / mutations in DNA

Question 2

Which genes do mutations occur in that lead to cancer?

Answer 2

mutations in

• Tumour suppressor genes causing them to be silenced
• Oncogenes being over-expressed

Question 3

What three things cause cancer cells to proliferate?

Answer 3

• Self synthesis of growth factors
• signal nearby cells to produce growth factors
• increase responsitivity to growth factors

Question 4

What protein do cancer cells develop that cause immune evasion?

Answer 4

Tumour cells contain a protein PD-L1 which effectively enables it to evade the immune system by down-regulating T cells

Bind to PD-1 receptor on the T- cell stopping it from attacking the cancerous cell

Question 5

What are the differences between a benign tumour and malignant tumour?

Answer 5

Benign:
Grows more slowly
Well-differentiated
Capsulated
Does NOT invade neighbouring tissue
Does NOT metastasize

Malignant:
Grows faster
Poorly differentiated
Not capsulated
Invades neighbouring tissue
Invades basement membrane and metastasizes

Question 6

What are three benign tumours of mesenchyme tissue?

Answer 6

Mesenchyme tissue
Osteoma (bone)
Chondroma (chondrocytes)
Angioma (blood vessels)

Question 7

What are two benign tumours of epithelial tissue?

Answer 7

Papilloma (lining epithelial)

Adenoma (gland)

Question 8

What is a malignant tumour of lymph nodes and blood cells?

Answer 8

Lymph nodes- Lymphoma

Blood cells- Leukaemia

Question 9

What are three malignant tumours of mesenchyme tissue?

Answer 9

Angiosarcoma
Osteosatcoma
Chondrosarcoma

Question 10

What are two malignant tumours of epithelial tissue?

Answer 10

squamous cell carcinoma

Adenocarcinoma

Question 11

What can cause cancer?

Answer 11

• Chemicals from smoking
• radiation can damage genes
• exogenous factors (virus introducing genes into cells)
• heredity, alterations in genes can make someone more susceptible to cancer and can be passed on to the next generation

Question 12

What did a study show that lifetime risk of developing cancer in a particular tissue correlates with?

Answer 12

Lifetime risk of developing cancer in a certain tissue correlates with how often stem cells divide in that tissue

Question 12

What did a study show that lifetime risk of developing cancer in a particular tissue correlates with?

Answer 12

Lifetime risk of developing cancer in a certain tissue correlates with how often stem cells divide in that tissue

Question 13

What is a germline mutation and can it passed onto offspring?

Answer 13

present in egg or sperm and are heritable, therefore can be passed onto offspring

rare 10% but every cell in the organism will contain that mutation, though tissue is affected at various levels

Question 14

What is a somatic mutation and can it passed onto offspring?

Answer 14

Occur in non germline tissues and are non-heritable
much more common (90%)

Usually, mutation in cancer genes accumulate in somatic cells over many years until a cell accumulate a sufficient number of errors to initiate the tumour.

Question 15

What is a passenger mutation?

Answer 15

Mutations a marker sign of cancer/driver mutations - many of these mutations can be tolerated by somatic cells

few mutations cause a selective advantage and are recurrently found

Mutations that provide no proliferative benefit

Question 16

What is a driver mutation?

Answer 16

Anything that contributes to cancer growth

Confer a fitness advantage to somatic cells in their microenvironment

Question 17

What are the 7 types of mutations?

Answer 17

deletions 
duplication 
Inversion 
translocation 
Single base substitution 
chromosome instability 
aneuploidy

Question 18

What is an oncogene? What do they result in?

Answer 18

Pro oncogene that mutates to become an oncogene - single mutation tends to be sufficient for cancer development

can result in an increase of some form of protein activity or loss or regulation

Question 19

What cellular processes does Ras protein control?

Answer 19

controls growth, migration, adhesion, cytoskeleton integrity, survival and differentiation

Question 20

What is the specific Ras oncogene that is mutated and what happens when it is mutated?

Answer 20

k-Ras

Cell proliferation is disrupted and the cell starts to divide in an uncontrolled manner

Question 21

What is the two hit hypothesis in cancer?

Answer 21

Situations where a form of genetic damage is not sufficient to enable cancer to develop (a second hit initiates cancer)
For example, a high degree of exposure to UV light may be required to initiate melanoma development.

Question 22

What chromosomal rearrangement can lead to CML?

Answer 22

Creation of fusion genes with oncogenic potential
Philadelphia chromosome formed by translocation - a specific chromosomal abnormality - It is the results of a reciprocal translocation between chromosome 9 and chromosome 22.
Creates an elongated chromosome 9 and a truncated chromosome 22
the resulting Philadelphia translocation fuses two genes BCR and abl.

Question 23

Give one function of retinoblastoma and explain how it carries out this function

Answer 23

Prevents excessive cell growth by inhibiting cell cycle progression until a cell has made all checks necessary in G1 phase

Question 24

What phosphorylates retinoblastoma leading to its inactivation?

Answer 24

Cyclin dependent kinase

Question 25

What does myc do?

Answer 25

transcription factor that increases expression of cyclins and cdks

Question 26

How does normal Rb work?

Answer 26

Rb protein normally inhibits cell proliferation by binding and inhibiting transcription factor E2F which promotes transcription of cyclin E and CDK 2

Rb is only active and inhibiting E2F when it isn’t bound to phosphate so when growth factor stimulates a growth signalling pathway it activates CDKs which add a phosphate to rb inhibiting it

phosphorylated Rb releases E2 allowing cell proliferation to occur

Question 27

What is the role of p53

Answer 27

P53 is a transcription factor that checks for DNA damage before a cell enters the S phase.

If there is damage, then specific protein kinases add phosphate groups to p53 - prolonging its life.

It binds to DNA and promotes transcription of a gene encoding protein called p21

p21 binds and inhibits the cyclin E-cyclin dependent kinase-2 protein complex, thus preventing passage from the G1 phase to S phase.

DNA repair proteins, also expressed thanks to p53 repairs the DNA damage

Question 28

What 3 possible states can a cell that has accumulated a large amount of DNA, or one that no longer effectively repairs damage incurred to its DNA enter into?

Answer 28

An irreversible state of dormancy

Cell suicide, AKA apoptosis (programmed cell death)

Unregulated cell division, which can lead to the formation of a tumour that is cancerous

Question 29

What virus is responsible for 99% of cervical cancer?

Answer 29

HPV (human papilloma virus) (However, not every viral infection leads to cancer and most HPV infections are lower risk and produce a localised disturbance)