Deck 23: Cancer Genetics

Question 1

Which cell cycle checkpoint is most responsible for the decision of the cell to commit to dividing?

A) the S/G₂ checkpoint
B) the G₁/S checkpoint
C) the spindle-assembly checkpoint
D) the G₂/M checkpoint
E) the G₁/G₂ checkpoint

Answer 1

B

Question 2

Which of the following types of cancer is associated with a defect in nucleotide-excision repair?

A) retinoblastoma
B) xeroderma pigmentosum
C) cervical cancer
D) chronic myelogenous leukemia
E) Bloom syndrome

Answer 2

B

Question 3

Most cancers are assumed to arise through which of the following?

A) errors in transcription
B) the production of unbalanced gametes because of nondisjunction during meiosis
C) genetic or epigenetic changes in somatic cells
D) delayed cell division during early embryogenesis
E) No correct answer is provided.

Answer 3

C

Question 4

The p53 gene is important in controlling apoptosis, but it also plays a role i:

A) initiating mitosis.
B) controlling cell adhesion.
C) opening ion channels.
D) duplicating the centrosome.
E) preventing aneuploidy by regulating the spindle-assembly checkpoint.

Question 5

Which of the following is a process whereby cancer cells travel to other sites in the body and establish secondary tumors?

A) oncogenesis
B) angiogenesis
C) malignancy
D) secondary tumorigenesis
E) metastasis

Question 6

An abnormally low level of expression of a particular microRNA might facilitate the development of a cancer by which of the following methods?

A) inducing the increased expression of a tumor-suppressor gene
B) inducing the increased expression of DNA-repair genes
C) promoting a decreased level of telomerase activity
D) inhibiting the G₁ to M transition in the cell cycle
E) increasing the expression of an oncogene

Question 7

Certain viruses are instrumental in converting proto-oncogenes to oncogenes. This conversion most commonly results because:

A) viruses specifically infect cells that contain proto-oncogenes.
B) only viruses contain genes that can convert proto-oncogenes into oncogenes.
C) the proto-oncogenes are more likely to undergo mutation or recombination within a virus.
D) viruses contain the remainder part of the DNA that is added to the proto-oncogene to form the oncogene.

Question 8

The process by which genetic changes occur in tumors and allows them to become increasingly aggressive over time is called:

A) clonal evolution.
B) metastasis.
C) loss of heterozygosity.
D) epigenetic evolution.
E) signal transduction.

Question 9

What is one line of evidence supporting the idea that cancer is influenced by environmental factors?

Question 10

Genes that encode components of the cytoskeleton and extracellular matrix often contribute to which of the following processes?

A) DNA repair
B) mutation
C) metastasis
D) primary tumor formation
E) signal transduction

Question 11

List three observations consistent with the idea that cancer arises through an accumulation of mutations in several genes that promotes cellular proliferation in single cells.

Question 12

Describe an example in which environmental factors interact with a genotype to produce cancer.

Question 13

Which of the following result(s) directly from metastasis?

A) primary tumors
B) secondary tumors
C) tumor vascularization
D) decreased DNA repair
E) increased apoptosis

Question 14

What specifically do most people inherit when they inherit a predisposition to a particular cancer such as retinoblastoma?

A) a mutation that causes the overexpression of a DNA repair gene
B) a mutation that causes telomerase to have reduced expression in somatic cells
C) a deleterious mutation in one copy of a tumor-suppressor gene
D) a deletion that removes one copy of an oncogene
E) an extra X chromosome from the mother

Question 15

Mutations in proto-oncogenes are generally _____ whereas mutations in tumor-suppressor alleles are generally _____.

A) deletions; duplications
B) recessive; dominant
C) duplications; deletions
D) dominant; recessive
E) deletions; base-pair substitutions

Question 16

Which of the following is the major event associated with the retinoblastoma cancer?

A) a translocation involving chromosomes 9 and 22
B) both copies of a tumor-suppressor gene being inactivated
C) a translocation resulting in the enhanced expression of an oncogene
D) a mutation resulting in an activated RAS oncogene
E) inactivation of a major DNA repair system

Question 17

If you were assigned a new form of cancer to study, you might want to determine whether it has a strong genetic basis or whether it is caused primarily by environmental factors. Propose some ways in which you could attempt to determine which hypothesis is correct. Which methods would be the easiest to use first?

Question 18

Evidence that the development of cancer is a multistep process includes the:

A) observation that certain tumor-suppressor genes and oncogenes are involved in a sequential manner in the development of colon cancer
B) fact that proto-oncogenes are widely conserved in evolution
C) usual occurrence of retinoblastoma at a young age
D) development of a cancer as a result of activation of a single oncogene by any of a variety of mechanisms
E) fact that there are many genetic and epigenetic mechanisms that lead to inactivation of the same tumor-suppressor gene

Question 19

Which of the following groups of proteins is NOT commonly known to include oncogenes?

A) transcription factors
B) growth factors
C) signal-transduction proteins
D) ion channels
E) growth factor receptors

Question 20

Which of the following are regulatory molecules whose normal function is to inhibit gene expression but which often have reduced activity in many tumor cells?

A) histones
B) miRNAs
C) reverse transcriptases
D) growth factors
E) kinases

Question 21

Most of the inherited forms of cancer involve a germline mutation in a tumor-suppressor gene while only a very few inherited cancers involve a mutation in an oncogene. What is the most reasonable explanation for this difference?

Question 22

Many tumor cells are able divide uncontrollably in cell culture in the laboratory. Some of these cell lines have genomes with a mutant tumor-suppressor gene. Adding a wild-type copy of this tumor-suppressor gene to the genomes of these cells reduces their ability to divide in culture. In contrast, adding a wild-type copy of a proto-oncogene to the genomes of a tumor cell line with an activated oncogene doesn't have any effect on the uncontrolled cell division shown by this line. Which of the following statements BEST explains why adding a wild-type proto-oncogene doesn't affect cell division in these cell lines?

A) Most point mutations that produce activated oncogenes are dominant gain-of-function mutations.
B) Many proto-oncogenes encode proteins that act to promote apoptosis.
C) Many proto-oncogenes encode proteins involved in DNA repair.
D) Many proto-oncogenes are inherited as recessive mutations.
E) Most protein products of proto-oncogenes don't have a role in cell division.

Question 23

The overexpression of certain microRNAs, called oncomiRs, is associated with some types of cancer. What type of gene is the likely target of these oncomiRs in cancer cells?

A) proto-oncogenes
B) tumor-suppressor genes
C) genes that promote angiogenesis
D) genes that allow the G₁/S transition
E) genes involved in DNA repair

Question 24

A rare situation where only one of the two copies of a particular tumor-suppressor gene needs to be inactivated before there is a progression toward cancer is called:

A) clonal evolution.
B) loss of heterozygosity.
C) signal transduction.
D) aneuploidy.
E) haploinsufficiency.

Question 25

_____ and _____ are chromosomal mutations that may activate cellular oncogenes by moving them to new regulatory sequences where they become overexpressed.

A) Duplications; deletions
B) Inversions; translocations
C) Duplications; inversions
D) Deletions; translocations
E) Aneuploidy; deletions

Question 26

A genetics student recently learned of the connection between telomerase and cancer. Curious as to whether he is at risk for developing cancer, he sneaks into a lab at night to analyze his DNA. He isolates DNA from his skin cells and applies PCR using primers specific to the telomerase gene. He runs a gel on his PCR reaction and sees that he has a PCR product on the gel. He is terrified because he knows this means he has the telomerase gene in his skin cells and thinks he will develop skin cancer. He takes his findings to his genetics professor. What does she tell him (besides he shouldn't be sneaking into a lab!)?

A) The telomerase gene should not be present in somatic cells; thus, he is at an increased risk of developing skin cancer and should take the results to his physician.
B) His results are normal because the telomerase gene should be present in all cells, including somatic cells. However, its expression should only be found in stem cells and germ cells. He should have looked at the expression levels of the gene, not the presence of the gene itself (and he should study more!).
C) His results are inconclusive because they cannot determine if the telomerase gene he amplified has a mutation in its coding sequence, which is what leads to cancer.
D) Telomerase mutations that result in cancer behave in a dominant manner. Therefore, rather than going through the effort of a genetic analysis, the student should have constructed a family pedigree to determine if members of his family had skin cancer, which could then determine his risk.
E) He should not be concerned about his cancer risk because transcriptionally active telomerase should be present in somatic cells to maintain the length of the chromosomes and thus prevent cancer.

Question 27

A cell is unable to progress into the S phase of the cell cycle. Further studies indicate that the RB-E2F complex is unable to dissociate in this cell and thus remains together. Which of the following genes is MOST likely mutated?

A) a gene that encodes a cyclin-dependent kinase
B) a gene that encodes an acetylase
C) a gene that encodes an enzyme that removes phosphate groups from RB
D) a gene that encodes an enzyme that phosphorylates E2F
E) a gene that encodes the Ras protein

Question 28

What are oncogenes and tumor-suppressor genes? How are they involved in carcinogenesis?

Question 29

The normal activity of the retinoblastoma (Rb) protein in the cell is to:

A) inhibit p53 activity.
B) suppress transcription of tumor-suppressor genes.
C) regulate the progression of from G₁ to S in the cell cycle.
D) induce cyclin-CDK complex formation.
E) block the initiation of anaphase during the cell cycle.

Question 30

Which of the following statements is TRUE concerning the function of proto-oncogenes?

A) They make products that act as signals to initiate cellular apoptosis.
B) Their products are components of cell growth pathways.
C) Proto-oncogenes make products that act as cell checkpoint regulators.
D) Proto-oncogenes make products that scan the genome for DNA damage.
E) Proto-oncogenes make products that repair DNA at sites of lesions.

Question 31

Use the following to answer questions
A new form of kidney cancer was identified in a family in which many of the family members were affected. This family's pedigree is shown below.
*
Upon genetic analysis of the cancerous tissue, a mutated form of a gene, named the kid gene, was discovered in all affected individuals but not in the unaffected individuals. Because so many members of the family are affected, the female (age 60), indicated with a "*", is concerned that although she has not developed the disease yet she still may develop the cancer later in life. What would a genetic counselor tell her?

A) All members of the family carry one mutant version of the kid gene, but those with cancer gained a second mutation of the kid gene. Therefore, it is highly likely that she will develop the kidney cancer.
B) While it is unlikely that she will develop the form of kidney cancer seen in her family, the mutant form of the kid gene she carries puts her at an increased risk of all types of cancer.
C) Because her parents did not develop kidney cancer, it is highly unlikely that they had a mutant form of the kid gene, and thus it is highly unlikely that she has a mutant kid gene. Therefore, she is not at risk of developing this form of kidney cancer.
D) While she carries a mutant copy of the kid gene, it is highly unlikely that she will develop kidney cancer because two mutant copies are required to be affected with the cancer.
E) Her father was a carrier of the mutant kid gene, and thus she is also a carrier of the mutant kid gene. She will likely not be affected, but her children will be at a high risk of developing the cancer.

Question 32

Consider the Ras signal-transduction pathway. Suppose a mutation occurred in the gene that encodes MEK that renders it nonfunctional. Which of the following effects would you see in this situation?

A) Binding of the growth factor to the receptor would occur, but the receptor's conformational change that is needed for the pathway to go forward would not occur.
B) Activated Ras would no longer have the ability to activate Raf, and the signal-transduction pathway would be halted at this step.
C) Ras would lose the ability to bind GTP and thus could no longer become activated, and the signal-transduction pathway would be halted at this step.
D) MAP kinase would not be activated and thus could not move into the nucleus to activate transcription factors.
E) Inactive Ras would move into the nucleus and inactivate tumor-suppressor transcription factors, which could ultimately result in cancer.

Question 33

List three ways in which proto-oncogenes can be converted to oncogenes by viruses.

Question 34

Why is it more difficult for researchers to identify tumor-suppressor genes than oncogenes?

Question 35

Normal cellular genes whose products are involved in facilitating cell division to occur under appropriate conditions are called:

A) proto-oncogenes.
B) tumor-suppressor genes.
C) passenger genes.
D) inhibitor genes.
E) driver genes.

Question 36

The increased levels of telomerase associated with many tumor cells likely promote cancer by:

A) enhancing levels of DNA repair so that cells remain normal and have stable genomes and thus would be able to replicate their DNA and divide more often.
B) promoting the efficiency of the spindle-assembly checkpoint.
C) reducing the expression of several oncogenes.
D) allowing cells to continue to divide when normally chromosomes should shorten beyond a point where division would be no longer possible.
E) decreasing the number of epigenetic changes that would promote cancer.

Question 37

Consider the Ras signal-transduction pathway. Suppose that a mutation occurred within the gene that encodes the transmembrane receptor protein. Which of the following types of mutations in this receptor could lead to cancer?

A) a mutation that allows the receptor to become phosphorylated in the absence of a growth factor bound to it
B) a mutation in the extracellular domain that prevents the binding of a growth factor
C) a mutation in the transmembrane domain that prevents the signal from being transduced to the interior of the cell
D) a mutation within the intracellular domain that prevents interaction with the adaptor molecules
E) All of these are types of receptors mutations that could lead to cancer.

Question 38

Mutant forms of tumor-suppressor genes typically behave in a recessive manner. However, a recent study of patients with multiple myeloma revealed that approximately 10% of these patients have one normal p53 gene and one mutant p53 gene. If it is the mutant p53 gene that is responsible for this group's cancer, which of the following statements would most likely be TRUE?

A) The p53 gene can act in a haploinsufficient manner.
B) The p53 gene is not a tumor-suppressor gene in these patients but rather an oncogene.
C) The mutant p53 gene most likely is involved in DNA-repair pathways.
D) The mutant p53 gene is having epigenetic effects in these patients.
E) The mutant p53 gene is being overexpressed in these patients.

Question 39

Use the following to answer questions
A new form of kidney cancer was identified in a family in which many of the family members were affected. This family's pedigree is shown below.
*
Upon genetic analysis of the cancerous tissue, a mutated form of a gene, named the kid gene, was discovered in all affected individuals but not in the unaffected individuals. What is the MOST likely function of the normal, nonmutated kid gene?

A) DNA-repair gene
B) proto-oncogene
C) tumor-suppressor gene
D) telomerase gene
E) acetyltransferase gene

Question 40

Many tumors exhibit:

A) abnormally high levels of telomerase expression.
B) abnormally high levels of tumor-suppressor gene expression.
C) translocations that move a tumor-suppressor gene to a new location that increases its normal expression.
D) deletions that remove an oncogene from the genome.
E) DNA replication that is inhibited when it would normally occur.

Question 41

Briefly describe the relationship among cyclins, cyclin-dependent kinases (CDKs), and cancer.

Question 42

How can defects in DNA-repair mechanisms lead to the development of cancer?

Question 43

A patient's cells from a colorectal polyp were collected and the APC and ras genes were analyzed. The APC gene was found to be mutated, and the ras gene was found to be up-regulated. The physician classifies the polyp an adenoma and advises the patient to have the polyp removed. The patient claims that the physician is incorrect in his advice to have the polyp removed. Is the physician's advice logical? Why or why not?

A) no, because adenomas are benign tumors and thus are unlikely to progress to a malignant tumor
B) no, because the up-regulation of the ras gene will counter the effects of the mutant APC gene, and the benign tumor is unlikely to progress to a malignant state
C) no, because until the specific function of the mutated APC gene is known, it cannot be determined that the cells are in a proliferative state
D) yes, because the cells of the polyp have already begun to divide inappropriately, and further mutations may allow the tumor to invade other tissues and metastasize
E) yes, because up-regulation of the ras gene is causing the cells to divide more slowly, and thus they will be unable to repair future DNA damage that will likely occur in cells surrounding the polyp

Question 44

Explain how DNA sequencing studies can aid in our understanding of cancer formation.

Question 45

Which of the following chromosomal abnormalities is associated with chronic myelogenous leukemia?

A) a deletion
B) an inversion
C) a duplication
D) a reciprocal translocation
E) an aneuploidy involving one of the shorter autosomal chromosomes

Question 46

In Burkitt lymphoma, there is increased expression of the MYC gene. Which of the following statements BEST explains the reason for the increased expression of this gene?

A) A chromosome deletion has removed a tumor-suppressor gene.
B) A chromosome deletion has removed an oncogene.
C) A chromosome duplication involves a segment with an oncogene.
D) A translocation has brought the MYC gene next to a different regulatory region.
E) The MYC gene has been amplified.

Question 47

Chromosome mutations are common in tumor cells. Do these mutations cause cancer, or are they a result of cancer? What evidence is there for your conclusion?

Question 48

Distinguish between driver and passenger mutations in cancer genomes. Propose a strategy whereby "knock-in" technology (Chapter 19) could be used to distinguish between driver and passenger mutations. What might be a major limitation to this strategy?

Question 49

A cancer cell line was identified as having inappropriate expression of telomerase. Which of the following would be the BEST treatment that could make this cell line mortal?

A) a drug that increases the levels of telomerase expression
B) a drug that methylates the promoter of the telomerase gene
C) a drug that repairs the mutation within the coding region of the telomerase
D) a drug that allows the telomerase to be expressed but at lower levels
E) a drug that inhibits a tumor-suppressor gene in the cell line

Question 50

What is angiogenesis? Why are mutations involving angiogenesis associated with tumors?

Question 51

What are the important checkpoints in the cell cycle?

Question 52

What are two processes that determine how quickly mutations accumulate within a cell?

Question 53

In cancer, mutations in stimulatory genes (such as in proto-oncogenes) are often dominant, whereas mutations in inhibitory genes (such as tumor-suppressor alleles) are often recessive. Why?

Question 54

What is unique to the DNA changes observed in the Apaf-1 gene in malignant melanoma cells? What are such changes to DNA called, and why do you think these types of changes in cancer have caught researchers' attention?

Question 55

Explain briefly why changes in oncogenes result in more rapid progression of a cancer compared to changes in tumor-suppressor genes. Mention one situation in which changes in a tumor-suppressor gene have a similar likelihood of causing cancer as changes in an oncogene.

Question 56

For each important checkpoint in the cell cycle, what must happen for the cycle to continue past the checkpoint?

Question 57

A headline in the June 12, 2009, issue of Science Daily proclaimed that "MicroRNA Replacement Therapy May Stop Cancer in Its Tracks." The article described a study in which a virus was used to deliver a microRNA gene to cancerous and noncancerous liver cells in mice. Aggressive liver tumors were stopped in their tracks in 8 out of 10 treated mice. Explain how delivery of a gene encoding microRNA might be able to reduce the growth of cancer cells.

Question 58

Which of the following statements BEST characterizes many cancers such as colon cancer?

A) They result from the activation of one critical tumor-suppressor gene.
B) They result when the transition from G₂ to M in the cell cycle is inhibited.
C) They result when DNA replication during the S period of the cell cycle is inhibited.
D) They result from a series of sequential mutations in a number of genes.
E) They result from decreased expression in a series of cellular oncogenes.

Question 59

Explain how hypermethylation and hypomethylation may be associated with cancers.

Question 60

Retinoblastoma (RB) protein is important in regulating the cell cycle. It must be completely phosphorylated before the cell can move from the G₁ phase to the S phase of the cell cycle. Retinoblastoma is a type of cancer. Based on this information, what do you think goes wrong in retinoblastoma?

Question 61

The Philadelphia chromosome is:

A) an example of an aneuploidy.
B) the result of a translocated chromosome involving parts of chromosomes 9 and 22.
C) a lengthened version of chromosome 22 that results from a recombination event with chromosome 12.
D) a shortened version of chromosome 22 that results from a deletion.
E) a lengthened version of chromosome 22 that results from a duplication.

Question 62

Briefly describe the role that the genes APC, p53, and Ras may have in the development of colon cancer.

Question 63

Which of the following is not a typical mechanism by which a proto-oncogene is converted to an oncogene?

A) a chromosomal translocation resulting in the bringing together of two different genes that make a fusion protein
B) a chromosomal translocation resulting in enhanced regulation of the proto-oncogene
C) complete deletion of the proto-oncogene
D) a point mutation in the proto-oncogene
E) All of these are mechanisms of converting proto-oncogenes to oncogenes.

Question 64

In Burkitt lymphoma patients, despite translocation, the oncogene c-MYC remains nearly intact in its new location. Yet c-MYC is believed to be responsible for the lymphoma because the c-MYC:

A) DNA sequence undergoes hypermethylation
B) DNA sequence is nearly intact but is inverted in the new position
C) gene is released from inhibition by miRNAs
D) gene is placed under the control of B-cell-specific gene regulatory sequences and is highly expressed
E) DNA sequence undergoes several point mutations

Question 65

Which of the following statements is FALSE?

A) Tumors usually show a clonal evolution.
B) Cervical cancer is associated with an animal virus.
C) Some cancers are associated with reduced DNA repair.
D) Epigenetic changes in somatic cells may be associated with some cancers.
E) Most tumors arise from germ-line mutations that accumulate during our life span.

Question 66

What is a possible effect of mutations in genes that influence chromosome segregation during division?

Question 67

The development of colon cancer is relatively well understood. Describe the steps of the development of colon cancer, including any genetic components.

Question 68

Human papilloma virus (HPV) is a DNA virus that is associated with cervical cancer. Despite the high prevalence of HPV in the population, the incidence of cervical cancer in the United States has decreased 75% in the past 40 years.
a. What are some reasons that cervical cancer has decreased in the United States?
b. How can cervical cancer rates be lowered in countries where the rates are still high?
c. Based on what you know about some different types of cancers and their genetic bases, can you suggest ways in which some of these other cancers might be addressed with respect to treatment and prevention?

Question 69

Consider the Ras signal-transduction pathway. Suppose a mutation occurred in the gene that encodes the transmembrane receptor to which a growth factor binds. The mutation no longer allows the growth factor to bind to the receptor. Which of the following methods could be used to overcome this mutation and allow the pathway to move forward?

A) Inject extremely high levels of growth factor into the cell.
B) Inject normal levels of nonmutated growth factor into the cell.
C) Inject only the growth factor binding domain of the transmembrane receptor into the cell.
D) Inject the activated form of Ras into the cell.
E) Inject nonmutated tumor-suppressor genes into the cell.

Question 70

Many viruses that are associated with cancers in animals are _____ that use reverse transcriptase.

A) papilloma viruses
B) Epstein-Barr viruses
C) retroviruses
D) hepatitis B viruses
E) None of the answers is correct.

Question 71

A routine colonoscopy detects a small colorectal polyp on the colon wall that has not reached adenoma status. Which of the following genes would you most likely predict to be mutated at this stage?

A) APC
B) p53
C) ras
D) antimetastasis gene

Question 72

Explain how retroviruses may cause cancers.

Question 73

A drug is injected into a cell that inhibits the removal of phosphate groups from MPF. Which of the following would result?

A) MPF would remain in its active state.
B) The cell would not be able to transition into mitosis.
C) Cyclin B levels would not be able to increase.
D) The cell would not be able to progress through the G₁/S checkpoint.
E) Cyclin D could no longer be activated.

Question 74

Which of the following would be the result of a mutation that inactivates cyclin-E?

A) inactivation of RB
B) inactivation of cyclin-D
C) inactivation of Ras
D) failure of the cell to progress through the G₂/M checkpoint
E) failure of E2F to bind to DNA and stimulate transcription