Deck 17: Medical Molecular Biology

Question 1

Which statement is not true about cancer?

A) Cancer results from the accumulation of many genetic changes.
B) Gene mutations that increase the risk for developing cancer are always inherited.
C) Cancer cells grow in an uncontrolled and invasive way.
D) Cancer cells are immortal.

Answer 1

Gene mutations that increase the risk for developing cancer are always inherited.

Question 2

The process by which cancer cells travel from the tissue of origin to other parts of the body is called

A) immortalization
B) transformation
C) metastasis
D) carcinogenesis

Answer 2

metastasis

Question 3

Can surgery successfully cure a patient of a cancer that has metastasized?

A) No; all the body cells of the patient are dividing uncontrollably.
B) Yes; surgery could remove all the patient's cells with defective cell-cycle regulation.
C) No; cancer cells are no longer localized in one spot in the patient.
D) Yes; if the patient's tumor is benign.

Answer 3

No; cancer cells are no longer localized in one spot in the patient.

Question 4

Cancer is a multi-step disease that requires

A) at least four to eight genetic changes over the course of years
B) mutation of the cancer gene
C) at least 20 genetic changes over the course of years
D) at least four to eight genetic changes over the course of days

Question 5

Chemical agents that cause cancer are known as

A) transformers
B) carcinogens
C) tumor suppressors
D) oncogenes

Question 6

What is a tumor suppressor gene?

A) A gene associated with tumor formation when its product does not function.
B) A gene associated with tumor formation when its product functions normally.
C) A gene that accelerates the cell cycle and leads to uncontrolled cell growth.
D) A gene that codes for a transcription factor involved in tumor formation.

Question 7

What is an oncogene?

A) A gene associated with tumor formation when its product does not function.
B) A gene associated with tumor formation when it is inappropriately activated.
C) A gene that inhibits cell growth when its product functions normally.
D) A gene that codes for a transcription factor involved in tumor formation.

Question 8

The c-src proto-oncogene encodes a membrane-associated, nonreceptor tyrosine kinase. The v-src oncogene product differs from c-Src in what way?

A) Because of amino acid substitutions in the C-terminus, the v-Src protein remains in theactive conformation and dephosphorylates target proteins.
B) Because of amino acid substitutions in the C-terminus, the v-Src protein remains in theactive conformation, binds to target genes and activates their expression.
C) Because of amino acid substitutions in the C-terminus, the v-Src protein remains in theinactive conformation and cannot phosphorylate target proteins.
D) Because of amino acid substitutions in the C-terminus, the v-Src protein remains in theactive conformation and phosphorylates target proteins.

Question 9

The c-myc proto-oncogene encodes a

A) helix-loop-helix transcription factor
B) nonreceptor tyrosine kinase
C) GTP-binding protein
D) secreted growth factor

Question 10

What would be the effect on cell growth if the retinoblastoma protein (pRB) remained phosphorylated?

A) pRB would prevent E2F from binding to regulatory elements in S phase-specific genes,resulting in an inhibition of cell growth.
B) The E2F complex would continue to stimulate S phase-specific genes, resulting in aninhibition of cell growth.
C) The E2F complex would continue to stimulate S phase-specific genes, resulting inunrestrained cell growth.
D) Cell growth would be normal because pRB is a phosphoprotein.

Question 11

What would be the consequence of inactivation of the E2F complex?

A) Cells would be unable to enter the S phase of the cell cycle.
B) Cells would immediately enter the S phase of the cell cycle.
C) Cells would rapidly proliferate and form a tumor.
D) The retinoblastoma protein (pRB) would become activated.

Question 12

Progression through the cell cycle is regulated by oscillations in the concentration of which factor?

A) cyclin-dependent kinases
B) cyclins
C) actin
D) tubulin

Question 13

If DNA damage occurs early in G1 of the cell cycle, the tumor suppressor protein p53

A) activates the p21 gene which encodes a CDK inhibitor, thereby causing G1 arrest.
B) promotes apoptosis.
C) phosphorylates the retinoblastoma protein (pRB), thereby blocking the cell cycle.
D) is targeted for degradation by the proteasome.

Question 14

In addition to promoting cell cycle arrest via cyclin/Cdk complexes in response to cytotoxic conditions such as DNA damage, the tumor suppressor p53 may

A) initiate programmed cell death.
B) induce the degradation of oncoproteins
C) stimulate translational arrest by phosphorylated eI $\alpha$ .
D) cause cells to stop growing by limiting glycolysis.

Question 15

Recent studies suggest that the expression pattern of a set of human _______ in cancer samples defines that cancer type better than microarray expression data from a set of 16,000 mRNAs.

A) snRNAs
B) snoRNAs
C) miRNAs
D) rRNAs

Question 16

The "Philadelphia chromosome" is a reciprocal translocation of chromosome 9 to 22, which causes chronic myelogenous leukemia. The chromosomal translocation fuses the genes encoding the tyrosine kinase ABL and BCR, an activator of ABL. The drug Gleevac has been shown to be effective in Phase II clinical trials. The drug works by:

A) dephosphorylating ABL substrates
B) blocking the active site of the ABL tyrosine kinase so that ATP cannot bind
C) binding to BCR in a way that inhibits its ability to activate ABL
D) degrading the ABL-BCR fusion protein

Question 17

Possible outcomes of DNA tumor virus infection are

A) lysis, cell death, and release of progeny viruses in permissive cells.
B) transformation of nonpermissive cells.
C) interaction between viral-encoded proteins and host cell proteins that inhibit their normaltumor suppressor function.
D) all of the above

Question 18

Tumor viruses can cause cancer by

A) encoding an oncogene
B) activating proto-oncogenes
C) activating retinoblastoma protein
D) A and B

Question 19

Which statement is not true about retroviruses (RNA tumor viruses).

A) Study of the oncogenes carried by retroviruses has led to major advances inunderstanding of the molecular basis of cancer.
B) Most human cancers are the result of a retroviral infection.
C) When a retrovirus infects a cell, its RNA genome is converted to DNA by the viral-encoded reverse transcriptase.
D) Occasionally retroviruses acquire a gene from the host that is normally involved in cellulargrowth control.

Question 20

The vast majority of human cervical cancers are associated with high-risk human papilloma virus (HPV). HPV is a

A) DNA tumor virus
B) RNA tumor virus
C) retrovirus
D) phage

Question 21

Benzo(a)pyrene can induce formation of DNA adducts that interfere with replication and transcription. It acts by a

A) promoter insertion mechanism
B) enhancer insertion mechanism
C) nongenotoxic mechanism
D) genotoxic mechanism

Question 22

Which type of gene therapy has not yet been tried in the clinic?

A) germline gene therapy
B) somatic cell gene therapy
C) ex vivo gene therapy
D) cancer gene therapy

Question 23

Which type of gene therapy involves genetic modification of gametes or embryos?

A) germline gene therapy
B) somatic cell gene therapy
C) ex vivo gene therapy
D) cancer gene therapy

Question 24

Which gene might be useful in the gene therapy treatment of cancer?

A) E2F
B) G1 cyclin
C) wild type proto-oncogenes
D) p53

Question 25

Currently, somatic cell gene therapy:

A) has only been tested in cell culture and animal models
B) is experimental and has never achieved any clinical success.
C) is experimental and has achieved only very limited clinical success.
D) is routine and has been used successfully to treat many diseases.

Question 26

With respect to gene therapy vectors, which of the following is the key advantage of liposomes over viruses?

A) They can be incorporated into endosomes.
B) They do not cause a host immune response.
C) Unlike viral vectors, they allow DNA to enter the host cell nucleus.
D) They enter cells more efficiently than viruses.

Question 27

To create a "safe" viral vector for delivery of genes into human cells, the virus must be engineered to:

A) remove all viral coat proteins.
B) remove all viral genes, replacing them with the human genes to be delivered.
C) remove select viral genes and replace them with the human genes to be delivered.
D) remove the viral genome and coat proteins and replace them with plasmids carrying the human genes to be delivered.

Question 28

The key step in the generation of "safe" (replication-incompetent) viral particles for gene therapy is

A) creation of site-specific mutations in viral genes
B) provision of viral genes on a ^- (psi^-) DNA
C) use of a packaging cell line that is not immortalized
D) deletion of the viral reverse transcriptase gene

Question 29

Adenovirus vectors for gene therapy have all of the following characteristics except:

A) they can infect both dividing and nondividing cells.
B) they have a larger capacity for foreign genes than other viral vectors.
C) they are very immunogenic
D) they stably integrate into host chromosomes

Question 30

Retrovirus vectors for gene therapy have all of the following characteristics except:

A) they can infect both dividing and nondividing cells.
B) they have a limited insert size.
C) they have generate only a mild immune response
D) they stably integrate into host chromosomes

Question 31

Which mode of gene therapy accomplishes transgene integration into the target cell's genome?

A) adenovirus-mediated
B) retrovirus-mediated
C) liposome-mediated
D) A and B

Question 32

Which is a present concern regarding the use of retroviral vectors for gene therapy?

A) They will integrate their DNA into the genome instead of remaining extrachromosomal DNA.
B) They will integrate their DNA into the genome in ways that disrupt or misregulate the expression of genes at or near the site of integration.
C) They will fail to introduce the therapeutic gene into any of the patient's cells.
D) They will cause retroviral disease.

Question 33

The most promising gene therapy clinical trial so far for cystic fibrosis used aerosol administration and

A) liposome-mediated gene transfer
B) adenovirus-mediated gene transfer
C) adeno-associated virus-mediated gene transfer
D) retrovirus-mediated gene transfer

Question 34

Current strategies for anti-HIV-1 gene therapy aim to do all of the following except:

A) destroy every cell infected with HIV-1
B) reduce plasma viral load
C) improve patient quality of life
D) use ribozymes to cleave viral RNA

Question 35

Which class of diseases is least amenable to treatment by gene therapy?

A) monogenic loss-of-function metabolic diseases
B) multigenic behavioral diseases
C) viral diseases
D) immunodeficiencies

Question 36

Distinguish between "oncogenes," "proto-oncogenes," and "tumor suppressor genes."

Question 37

Does the "two hit" hypothesis explain the role of oncogenes and proto-oncogenes in cancer? Why or why not?

Question 38

Draw a diagram illustrating how inappropriate activation of proto-oncogenes may be due to qualitative or quantitative changes.

Question 39

Describe the functional differences between c-Src and v-Src.

Question 40

Describe the three major roles of c-Src in cancer cell metastasis.

Question 41

Explain why c-myc is referred to as a central "oncogenic switch."

Question 42

Using retinoblastoma as an example, explain Knudson's "two-hit" hypothesis.

Question 43

What would be the effect on cell growth if the retinoblastoma protein (pRB) remained phosphorylated? Explain your answer.

Question 44

After activation of wild-type p53 in response to DNA damage, what are two possible outcomes of p53 activity?

Question 45

Explain how deletions of both alleles of p53, or missense point mutations in one allele, can each lead to unrestrained cell growth.

Question 46

Discuss recent evidence suggesting a role for microRNAs (miRNAs) in cancer progression.

Question 47

Explain the molecular mechanism for control of chronic myelogenous leukemia by imatinib mesylate (Gleevac).

Question 48

Diagram a model for human papilloma virus (HPV)-induced cervical cancer.

Question 49

Diagram the two main mechanisms for transformation of cells by retrovirus infection.

Question 50

Compare and contrast genotoxic and nongenotoxic effects of carcinogens.

Question 51

Diagram the pathway of tumor promotion by dioxin through arylhydrocarbon receptor-mediated signal transduction.

Question 52

In gene therapy clinical trials using retrovirus and adenovirus vectors, the levels of gene expression have generally been disappointingly low or transient. Based on your knowledge of these vectors and of the regulation of eukaryotic gene expression, provide an explanation for why this is the case.

Question 53

If you were attempting for the first time to develop a viral gene therapy for a monogenic disease, what factors would you need to consider in your selection of a vector? Explain your answer.

Question 54

Compare and contrast in vivo and ex vivo somatic cell gene therapy approaches.

Question 55

Explain why a "packaging cell" step is used when preparing a retroviral vector for gene transfer.

Question 56

Compare and contrast the strategies used for the treatment of ornithine transcarbamylase (OTC) deficiency, adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), and cystic fibrosis. Why are different treatment strategies and different vectors used for different genetic diseases?

Question 57

Why were gene therapy trials for SCID-X1 recently suspended despite very encouraging initial results of clinical trials?

Question 58

Diagram the HIV-1 life cycle and indicate some of the popular targets for antiviral strategies.

Question 59

Diagram the hypothesized action of a hairpin-derived catalytic antisense RNA against the HIV-1 long terminal repeat (LTR).

Question 60

Can gene therapy be used for purposes other than treatment of "monogenic" diseases (e.g., cystic fibrosis)? Explain your answer.

Question 61

You suspect that a gene you have cloned is a proto-oncogene. Describe how you would test your hypothesis experimentally. Predict the results.

Question 62

DNA microarray analysis reveals no expression of the pRB tumor suppressor gene in a bone cancer cell line. Would you expect this to be the only difference in expression pattern between normal and bone cancer cells. Why or why not?

Question 63

Analysis of another cell line reveals normal expression levels of pRB and yet the cells exhibit unrestrained cell growth. Provide an explanation and suggest how to test your hypothesis.

Question 64

As they light up their cigarette, a friend of yours tells you that they have heard that benzo(a)pyrene in cigarette smoke is not really a carcinogen. Set them straight.

Question 65

You are designing a somatic cell gene therapy protocol for spinal muscular atrophy, a genetic disorder that is caused by a defect in the Survival of Motor Neurons (SMN) gene. You have cloned the SMN cDNA.
(a) What is the minimal cis-acting DNA regulatory element you would need to ligate to the SMN cDNA to get transcription of the cDNA in cells?
(b) Assume that you decide to use retroviral-mediated gene transfer to introduce the SMN cDNA into the patient's target cells ex vivo. What are the advantages and disadvantages of this choice of vector for gene delivery? Is there another vector that would work better?