Genetics of Cancer

Question 1

What are the common features of cancer?

Answer 1

Somatic cells accumulate mutations in a variety of genes
Normal function of these genes is to act as accelerators or brakes for cell division
Mutations cause cancer cells to divide rapidly and uncontrollably

Question 2

What are the three ways cancer cells evade normal controls on cell growth?

Answer 2

Produce cell division signals (autocrine stimulation?
Lose contact inhibition
Avoid programmed cell death

Question 3

How many divisions do normal cells undergo before death?

Answer 3

20-50

Question 4

How is the length of chromosome ends maintained in cancer cells?

Answer 4

Expression of telomerase

Question 5

What is angiogenesis?

Answer 5

Production of substances that encourage blood vessel growth

Question 6

What is metastasis?

Answer 6

Blood vessels provide nutrients to tumor, allow movement to other locations

Question 7

Why do cancer cells have a higher rate of mutation than normal cells?

Answer 7

Enzymatic systems that repair DNA damage or mistakes during replication are often defective

Question 8

How is cancer correlated with old age? What does this support?

Answer 8

INcidence of cancer rises dramatically with age
Supports idea that cancer involves the accumulation of mutations in the clonal descendants of a somatic cell

Question 9

Why does inheritance of some mutations predispose a person to cancer?

Answer 9

They have to accumulate fewer mutations

Question 10

What are passenger mutations?

Answer 10

Occur due to increased mutation rate of cancer cells
Do not contribute to disease

Question 11

What are driver mutations?

Answer 11

Cause cancer phenotypes

Question 12

Which is more common in cancer genomes, passenger or driver mutations?

Answer 12

Passenger

Question 13

What needs to happen in order for cancer to appear?

Answer 13

Accumulation of several driver mutations in different genes

Question 14

How does feedback result in tumor progression?

Answer 14

Mutation result in more cancer-like properties
Cells with more cancer-like properties accumulate more mutations

Question 15

What are mitogens?

Answer 15

Growth factors that stimulate cell proliferation

Question 16

What are receptors?

Answer 16

Found on surface of cell
Bind growth factors
Initiate signal transductioncascade
Ultimately activates synthesis of transcription factors

Question 17

What are transcription factors?

Answer 17

Regulate genes whose protein products cause cells to divide or stop dividing

Question 18

What are the two basic types of signals that initiate cell division?

Answer 18

Extracellular and cell-bound

Question 19

What are extra-cellular signals?

Answer 19

Act over long or short distances

Question 20

What are extracellular signals collectively known as?

Answer 20

Hormones

Question 21

What are cell-bound signals?

Answer 21

Require direct contact between cells

Question 22

Give an example of an extracellular signal that acts over large distances

Answer 22

Thyroid-stimulating hormone (TSH) produced in pituitary gland
Moves through blood to thyroid gland, which expresses throxine, which influences metabolic rate

Question 23

How do growth factors transmit signals into cells?

Answer 23

Through transmembrane receptors

Question 24

What relays a signal transmitted into a cell?

Answer 24

Signal transducers

Question 25

What are oncoproteins?

Answer 25

Receptors that normally bind growth factors and do not require growth factor to be active. Retain their functionality but no longer respond to normal regulatory cell signals

Question 26

What are CDKs?

Answer 26

Family of kinases that regulate the transition through stages of the cell cycle

Question 27

When do CDKs function?

Answer 27

When associated with Cyclins

Question 28

What does phosphorylation by CDKs do?

Answer 28

Activate or inactivate proein

Question 29

What activates the G1 to S checkpoint?

Answer 29

DNA damage

Question 30

how is p53 related to apoptosis?

Answer 30

If DNA damage is great enough, cells producing p53 not only arrest in G1, but commit apoptosis

Question 31

Outline apoptosis

Answer 31

DNA is degraded, nucleus condenses, phagocytic cells devour and destroy dying cell

Question 32

What are checkpoints need?

Answer 32

They are not essential for cell division but cells with defective checkpoints are more vulnerable to DNA damage

Question 33

What are the three types of genomic instability checkpoints helps prevent transmission of?

Answer 33

Point mutations Translocations Gene amplification

Question 34

What is a proto-oncogene?

Answer 34

Nonmutant allele

Question 35

What proteins do proto-oncogenes often encode?

Answer 35

Those needed for cell cycle progression

Question 36

When are oncogenes produced?

Answer 36

When mutations cause improper activation in a gene

Question 37

What are two approached to identifying oncogenes?

Answer 37

Tumor-causing viruses Tumor DNA

Question 38

Outline how oncogenes can be identified through association with tumor viruses

Answer 38

After infection, retroviral genome integrates into host genome and may activate a proto-oncogene Genes near viral integration sites in cancer cells may be oncogenes Host proto-oncogenes may be packaged into RNA virus particles

Question 39

How can oncogenes be identified through cell transformation assays?

Answer 39

Human gene that is oncogenic can be identified and clone from transformed mouse cells

Question 40

Give examples of oncogenes

Answer 40

Ras, c-ABL, Her2

Question 41

Describe Ras

Answer 41

Usually active when bound to growth factor Onocgenic point mutation makes constitutively active protein

Question 42

Describe c-Abl

Answer 42

Chromosomal translocation fuses the c-abl and bcr genes hybrid protein encodes a constitutively active tyorsine kinase

Question 43

Describe Her2

Answer 43

FOund in 20% of breast cancers Ocerexpressed growth factor receptor

Question 44

Give an example of an ancient cancer treatment

Answer 44

Egpytian physicians treated it with surgery or sticking hot pokers into tumors

Question 45

What is chemotherapy

Answer 45

Drugs that may kill cancer cells that are unreachable or missed by surgery

Question 46

What does chemotherapy do?

Answer 46

Directed against pathways needed for cell proliferation

Question 47

What is an issue with chemotherapy?

Answer 47

Our bodies require cell renewal Normal proliferating cells are killed by chemotherapy

Question 48

Explain how Gleevec works

Answer 48

ATP required for Bcr/c-Abl enzyme to phosphorylate target proteins Gleevec binds to the ATP binding site, inactivating enzyme Leukemic blood cells disappeard in 98% of patients

Question 49

Explain Herceptin

Answer 49

Antibody that binds to the Her2 receptor Prevents activation Results in destruction of cancer cells

Question 50

What are some challenges with counteracting mutations in tumor suppressor genes?

Answer 50

Cancer cells lack both functional copies of tumor suppressor genes - nothing to tatger

Question 51

What are two cancer therapies that increase the ability of T cells to destroy cancer cells?

Answer 51

Blocking T-cell inhibitoris CAR T-cell therapy

Question 52

Explain blocking T-cell inhibitors

Answer 52

Some cancer cells avoid immmune system by using immune checkpoints PD-1 protein off switch on T cells prevents T cells from attacking normal body cells when bound by the PDL-1 protein on normal body cells Some cancer cells also express PDL-1, switching the PD-1 protein to off Antibodies against PD-1 or PDL-1 can act as cancer drugs, allowing T cells to attack cancer cells, but can have sever side effects

Question 53

Explain CAR T-cell therapy

Answer 53

A gene encoding a synthetic chimeric antigen receptor (CAR) is added to a pateint's T cells Receptor is designed to bind antigens on cancer cells but not normal cells Allows CAR T cells to destroy tumor cells