Chapter 16: Cancer Genetics

Question 1

What is cancer?

Answer 1

• Heterogeneous group of disorders characterized by the abnormal proliferation of cells that do not respond to the normal controls of division
• Creation of tumors that crowd out normal cells

Question 2

What chromosome abnormalities do cancer cells often possess?

Answer 2

• Extra chromosomes
• Missing chromosomes
• Chromosome rearrangements

Question 3

What occurs to tumor cells through clonal evolution?

Answer 3

Acquire multiple mutations that allow them to become increasingly aggressive and proliferative

Question 4

What may tumor cell mutations be favoured by, predisposing certain individuals?

Answer 4

Environmental conditions or heredity

Question 5

Differentiate benign and malignant tumors.

Answer 5

• Benign: if the tumor cells remain localized

- Malignant: if the cells invade other tissues

Question 6

What are issues with the genetic theory of cancer?

Answer 6

• If cancer is inherited, all cells should receive cancer-causing genes, and every cell should be cancerous
• Tumors only appear when a person reaches advanced age
• Many cancers do not run in families at all

Question 7

What is the multistep model of cancer? How does it relate to inheritance?

Answer 7

• Cancer is the result of a multistep process that requires several mutations
• If one or more of the required mutations are inherited, fewer additional mutations are required to produce cancer

Question 8

What mechanisms are normally eliminated in cancer cells?

Answer 8

DNA-repair mechanisms, which increases their chances at retaining mutations

Question 9

Explain the significance of colorectal cancer as an example of the multistep model?

Answer 9

• A polyp forms on the colon wall due to a mutation in the tumor-suppressor gene APC
• Activation of the ras oncogene creates an adenoma
• Mutation in p53 causes a carcinoma (malignant tumor) to develop

Question 10

Differentiate the major function of oncogenes and tumor-suppressor genes.

Answer 10

• Oncogenes: involved in cell growth

- Tumor-suppressor genes: involved in cell division

Question 11

What do proto-oncogenes normally produce? What about mutant alleles of oncogenes?

Answer 11

• Proto-oncogenes normally produce factors that STIMULATE cell division
• Mutant alleles induce excessive cell proliferation (hyperactive stimulatory factor)

Question 12

Are mutant alleles of oncogenes dominant or recessive? What does that mean?

Answer 12

• Mutant oncogenes are dominant

- One copy of the mutant allele is sufficient to induce excessive cell proliferation

Question 13

What do tumor-suppressor genes normally produce? What about mutant alleles of oncogenes?

Answer 13

• Normally produce factors that INHIBIT cell division

- Mutant alleles induce excessive proliferation (no inhibitory factor)

Question 14

Which genes produce an inhibitory factor?

Answer 14

Tumor-suppressor genes

Question 15

Which genes produce a stimulatory factor?

Answer 15

Oncogenes

Question 16

Are mutant alleles of tumor-suppressor dominant or recessive? What does that mean?

Answer 16

• Mutant tumor-suppressor genes are recessive

- Both alleles must be mutated to produce excessive cell proliferation

Question 17

Why are oncogenes usually dominant in their action, whereas tumor-suppressor genes are recessive?

Answer 17

• Oncogenes stimulate cell proliferation; mutations in a single copy of the gene is sufficient to produce a hyperstimulatory effect
• Tumor-suppressor genes inhibit cell proliferation; mutations in both copies of the gene is required to remove all inhibition

Question 18

What are cyclin-dependent kinases (CDKs)?

Answer 18

• Enzymes that phosphorylate other proteins
• Require a cyclin protein, which specifies which protein will phosphorylate
• Key events of the cell cycle are controlled by CDKs

Question 19

What is the function of the retinoblastoma (RB) protein? How does it function? At which checkpoint does it function?

Answer 19

• G1/S checkpoint

- The cell is prevented from passing through the checkpoint by RB, which binds to E2F to keep it inactive

Question 20

How are CDKs related to RB?

Answer 20

By late G1, CDKs phosphorylate RB to release E2F

Question 21

What is the function of released E2F?

Answer 21

• Stimulates the transcription of genes that produce enzymes necessary for replication of DNA
• Cell moves into the S phase of the cell cycle

Question 22

What occurs when the RB protein is mutated?

Answer 22

• Cells pass through the G1/S checkpoint without the normal controls that prevent cell proliferation
• E2F is constantly bound to the promoter

Question 23

What is the progression through the G1/S checkpoint regulated by?

Answer 23

RB protein

Question 24

What is the progression through the G2/M checkpoint regulated by?

Answer 24

Cyclin B

Question 25

What is the function of cyclin B?

Answer 25

• Cyclin B increases at G2
• Cyclin B dephosphorylates inactive MPF, rendering it active
• Active MPF (mitosis-promoting factor) allows mitosis to occur

Question 26

What occurs when the cyclin B is mutated?

Answer 26

If cyclin B is not degraded, the activating factor is constantly dephosphorylated, promoting abnormal cell proliferation

Question 27

Which type of mutation in telomerase can be associated with cancer cels?
A) Mutations that produce an inactive form of telomerase
B) Mutations that decrease the expression of telomerase
C) Mutations that increase the expression of telomerase
D) All of the above

Answer 27

C) Mutations that increase the expression of telomerase

Question 28

What would be the most likely effect of a mutation that causes cyclin B to be unable to bind to CDK?
A) Cells pass through the G2/M checkpoint and enter mitosis even when DNA has not been replicated.
B) Cells never pass through the G1/S checkpoint.
C) Cells pass through mitosis more quickly than unmutated cells.
D) Cells fail to pass the G2/M checkpoint and do not enter into mitosis

Answer 28

D) Cells fail to pass the G2/M checkpoint and do not enter into mitosis