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Pierce Test Bank Chapter 23

Chapter 23
Cancer Genetics
1. Most cancers arise from defects in DNA. (T)
2. The presence of a single mutated gene is sufficient for retinoblastoma cancer
to develop. (F)
3. miRNAs play a critical role in initiating tumor development. (F)
4. A single gene mutation may predispose a person to developing cancer. (T)
5. Overactive telomerase enzyme deletes the ends of chromosomes and can
cause cancer. (F)
6. Relatively few people inherit all of the genetic changes that cause cancer. (T)
7. Proto-oncogenes do not cause cancer. (T)
8. Most tumors arise from germ-line mutations that accumulate during our life
span. (F)
9. Xeroderma pigmentosum includes predisposition to cancer due to defects in a
specific DNA repair system. (T)
Fill in the Blank
10. Extra chromosomes, missing chromosomes, and chromosome
rearrangements are the chromosome abnormalities that are typically found in
advanced tumor-containing cells.
11. Many viruses that are associated with cancers in animals are retroviruses,
which use reverse transcription.
12. Telomeres normally shorten with cell age and are therefore involved in
regulating the life span of a cell, so mutations that prevent this shortening may
contribute to the lack of normal apoptosis in some cancer cells.
Cancer Genetics
13. Inversions and translocations are chromosomal mutations that may
inactivate tumor-suppressor alleles by preventing production of a functional
product or by moving genes relative to regulatory sequences.
14. Haploinsufficiency occurs when a single mutation of a normally recessive
allele in a cell is enough to cause the recessive trait to occur in the heterozygote.
15. Genetic changes in tumors that allow them to become increasingly
aggressive over time is called clonal evolution.
16. Mutations in proto-oncogenes are generally dominant, whereas mutations in
tumor-suppressor alleles are generally recessive.
17. The expression of miRNAs—regulatory RNAs that can inhibit gene
expression—is reduced in many tumor cells.
Multiple Choice
18. 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
19. Which of the following result(s) directly from metastasis?
a. primary tumors
*b. secondary tumors
c. tumor vascularization
d. cancer
e. malignancy
20. 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
*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 protooncogene to form the oncogene.
21. In Burkitt lymphoma patients, despite translocation, the oncogene c-MYC
remains intact in its new location. Yet c-MYC is believed to be responsible for the
lymphoma because:
a. the c-MYC DNA sequence undergoes hypermethylation.
Chapter 23
b. the c-MYC DNA sequence is intact but is inverted in the new position.
c. the c-MYC gene is released from inhibition by miRNAs.
*d. the c-MYC gene is placed under the control of B-cell-specific gene regulatory
22. Which of the following groups of proteins is NOT commonly known to include
a. transcription factors
b. growth factors
c. signal-transduction proteins
*d. ion channels
e. DNA-repair enzymes
23. Genes that encode components of the cytoskeleton and extracellular matrix
often contribute to which process?
a. angiogenesis
b. mutation
*c. metastasis
d. primary tumor formation
24. The p53 gene is important in controlling apoptosis, but it also plays a role in:
a. initiating mitosis.
b. controlling cell adhesion.
c. opening ion channels.
*d. duplicating the centrosome.
e. preventing aneuploidies by regulating the spindle-assembly checkpoint.
25. The Philadelphia chromosome is:
a. an example of an aneuploidy.
*b. a shortened version of chromosome 22 that results from a translocation.
c. a lengthened version of chromosome 22 that results from a translocation.
d. a shortened version of chromosome 22 that results from a deletion.
e. a lengthened version of chromosome 22 that results from a duplication.
26. Which cell cycle checkpoint is responsible for the initial decision of the cell to
a. the S/G2 checkpoint
*b. the G1/S checkpoint
c. the spindle-assembly checkpoint
d. the G2/M checkpoint
27. Match each of the three genes with the process it normally regulates and
then place the genes in the order in which they change during the progression of
colorectal cancer: p53; APC; ras; signals growth-factor stimuli to the nucleus;
regulates the rate of cell division; regulates proper chromosome segregation.
Cancer Genetics
regulates the rate of cell division
signals growth-factor stimuli to the nucleus
regulates proper chromosome segregation
Short Answer
28. 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?
The unique change is that the promoter of this gene is hypermethylated,
yet the DNA sequence and the location of Apaf-1 in the chromosome
remain unchanged. Reversibly modifying DNA without altering its
sequence is called an epigenetic change. Because an epigenetic change to
DNA involves no sequence or gross chromosomal changes, the cancerous
alteration may be amenable to drug therapy, a possibility that has inspired
interest among researchers who aim to control this type of cancer.
29. What is one line of evidence supporting the idea that cancer is influenced by
environmental factors?
There are significant differences in the incidences of specific cancers
around the world, and studies show that immigrants to a country will, over
time, tend to exhibit the cancer incidence of their host country, regardless
of differences in the cancer rate in their country of origin.
30. What are oncogenes and tumor-suppressor genes? How are they involved in
The control of the cell division cycle is regulated by stimulatory genes
(oncogenes) and inhibitory genes (tumor-suppressor genes), and
mutations in either type can lead to cancer by deregulating the cell cycle.
Mutations in an oncogene can lead to an overactive cellular process,
resulting in unregulated cellular proliferation. A defective tumorsuppressor gene can lead to the same result by blocking the activation of a
critical “braking” process necessary for the appropriate control of cellcycle progression.
31. List three observations consistent with the idea that cancer arises through an
accumulation of multiple mutations promoting cellular proliferation in single cells.
When single tumors are dissected and carefully analyzed, tumor cells
typically contain anomalies in several different chromosomes.
Several different tumor-suppressor genes have been shown to encode
enzymes necessary for DNA repair.
Chapter 23
Retinoblastoma, a cancer of the retina, usually occurs in only one eye.
The rare cases in which retinoblastoma affects both eyes are typically
found among individuals who have already inherited one genetic
defect. One explanation for both observations is that two (or more)
mutations must occur to cause retinoblastoma. The frequency of these
multiple mutations occurring in the same eye cell is so low that most
people have zero or only one founder cancer cell among the millions
of cells in their two eyes. But the frequency of two mutations in one
eye cell is higher when an inherited defect (mutation) is already
present in every eye cell, leading more frequently to more than one
founder cancer cell per individual and a higher probability that both
eyes will be affected.
32. List three ways in which proto-oncogenes can be converted to oncogenes by
(1) The sequence of the proto-oncogene may be altered or truncated when
the proto-oncogene is incorporated into the viral genome. The mutated
gene could then produce an aberrant protein product that triggers
uncontrolled cell proliferation when the virus invades another cell.
(2) Through recombination, a proto-oncogene may become juxtaposed next
to a new promoter or enhancer, which can then cause the gene to be
(3) The function of a proto-oncogene in the host cell may be altered when
viral DNA inserts into the gene. The mutated gene could then produce
an aberrant protein product that triggers uncontrolled cell proliferation.
33. Why is it more difficult for researchers to identify tumor-suppressor genes
than oncogenes?
Tumor-suppressor genes inhibit cancer and are therefore recessive — both
alleles must be mutated before the inhibition of cell division is reversed.
Because it is the loss of function in tumor-suppressor genes that promotes
cell proliferation and cancer, these genes cannot be identified by the
simple gain-of-function tests used for identifying oncogenes (introducing
the gene into normal cells and screening for a cancerous response).
34. Briefly describe the relationship among cyclins, cyclin-dependent kinases
(CDKs), and cancer.
Cyclins and CDKs play critical roles in regulating the cell cycle. Cyclin
concentration oscillates during the cell cycle, whereas the concentration of
CDKs remains relatively constant. Cyclins bind and then activate CDKs to
initiate key events in the cell cycle. Thus genes that code for cyclins and
for factors that stimulate the formation of activated CDKs are often
oncogenes. Genes that inhibit the formation of activated CDKs are good
candidates for tumor-suppressor genes. Mutated cyclin genes have been
Cancer Genetics
shown to be associated with various forms of cancer, and genes that
encode inhibitors of CDKs are mutated or missing in many cancer cells.
35. What are two processes that determine how quickly mutations accumulate
within a cell?
DNA replication and DNA repair are two processes that determine how
quickly mutations accumulate within a cell. Mutations occur as a result of
errors in replication but can be corrected afterward by DNA polymerase
and by other repair systems. Increases in the rate of errors, decreases in
the rate at which errors are corrected, or both can lead to increases in the
rate at which mutations accumulate within a cell.
36. In cancer, mutations in stimulatory genes (such as in proto-oncogenes) are
often dominant, whereas mutations in inhibitory genes (such as tumorsuppressor alleles) are often recessive. Why?
One source is sufficient to create a new stimulus. Thus, only one copy of a
stimulatory gene need be mutated. For example, if a proto-oncogene is
activated when it shouldn’t be, the new oncogene stimulates cell division
even if a remaining normal copy of the proto-oncogene does not. On the
other hand, to remove an existing, inhibitory signal requires removing all
sources of the signal. When one copy of an inhibitory gene is mutated and
stops functioning (i.e., stops inhibiting normally), the remaining copy of the
inhibitory gene can still provide some inhibition.
37. Explain how retroviruses may cause cancers.
Retroviruses are RNA viruses that use reverse transcriptase to make a DNA
copy that can integrate into the host chromosome. Retroviruses can (1)
mutate host genes when inserted and (2) alter the expression of host genes
(for example, by inserting promoters).
38. Explain how hypermethylation and hypomethylation may be associated with
Hypermethylation of DNA correlates with decreased expression of genes in
the methylated region. Tumor-suppressor alleles may be inactivated.
Hypomethylation is less clearly understood but may contribute to higher
mutation rates by causing increased chromosome instability.
39. What are the important checkpoints in the cell cycle?
The G1/S checkpoint is at the end of the G1 phase of the cell cycle.
The G2/M checkpoint is at the end of the G2 phase of the cell cycle.
The spindle-assembly checkpoint is in metaphase of mitosis.
Chapter 23
40. For each important checkpoint in the cell cycle, what must happen for the
cycle to continue past the checkpoint?
The G1/S checkpoint is at the end of the G1 phase of the cell cycle. The cell
cannot pass this checkpoint until retinoblastoma (RB) protein is completely
phosphorylated, inactivating it. This releases E2F protein, formerly bound
to RB protein. E2F protein is a transcription factor needed for the
expression of genes required for DNA replication. These genes are
required for DNA to be replicated in the S phase of the cell cycle. (Students
may add that cyclin D and cyclin E increase in concentration and associate
with cyclin-dependent kinases during G1; cyclin-D-CDK and cyclin-E-CDK
phosphorylate RB.)
The G2/M checkpoint is at the end of the G2 phase of the cell cycle.
Mitosis-promoting factor (MPF) is activated and gradually increases in
concentration. MPF phosphorylates other proteins, leading to changes
associated with mitosis (breakdown of the nuclear membrane, etc.).
(Students may add that cyclin B combines with CDK to form MPF.)
The spindle-assembly checkpoint does not allow mitosis to continue past
metaphase until all of the chromosomes are properly lined up on the
metaphase plate. (Students may add that cyclin B is not destroyed until the
chromosomes are properly lined up. This causes MPF to remain active.
MPF levels increase and promote mitosis through metaphase, then
decrease as the cell returns toward interphase.)
41. Retinoblastoma (RB) protein is important in regulating the cell cycle. It must
be completely phosphorylated before the cell can move from the G1 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?
Retinoblastoma is one example of several cancers that involve problems
with the G1/S checkpoint. In this form of cancer, the RB protein does not
work properly, and the cell continues past the checkpoint regardless of
whether it is ready to do so.
42. What is a possible effect of mutations in genes that influence chromosome
segregation during division?
This can lead to aneuploidies.
43. What is angiogenesis? Why are mutations associated with angiogenesis
associated with tumors?
Angiogenesis is the formation of blood vessels. Mutations associated with
angiogenesis can allow excessive blood vessel formation, providing
oxygen and nutrients to tumor cells.
Cancer Genetics
44. How can defects in DNA-repair mechanisms lead to the development of
Defects in DNA-repair mechanisms increase mutation rates, increasing the
probability of a mutation that could lead to cancer.
45. 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.
Oncogenes are dominant-acting cell-division stimulatory genes, while
tumor-suppressor genes are recessive cell-division inhibitory genes. A
single mutation in DNA is sufficient to give rise to an oncogene, but two
mutations in the same tumor-suppressor gene are required to remove
inhibition of cell division. Therefore, changes in oncogenes result in a more
rapid progression of cancer.
If an organism is predisposed to cancer by inheriting one mutant copy of a
tumor-suppressor gene, then it has to acquire only one mutation, similar to
an oncogene, before resulting in cancer.
(The following answer is also OK for the second part of the question:)
In some cases, haploinsufficiency of a tumor-suppressor gene cannot be
tolerated, or organisms with this condition are more likely to develop
cancer because other factors may combine with the lowered tumorsuppressor product to cause cancer.
46. 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
Chromosome mutations may be both causes and effects of cancer. Some
particular mutations are always associated with a particular cancer,
suggesting that the mutation causes that type of cancer. However, there
are also varied chromosomal mutations that are not specifically linked with
certain cancers. This suggests that genetic instability is a general feature
of these cells and is an effect, rather than a cause, of the disease.
47. 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.
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(A) What are some reasons that cervical cancer has decreased in the United
A major reason has been the increased use of Pap tests to detect early
precancerous and cancerous growth, allowing time for effective treatment.
Vaccination may further lower the rate in future years.
(B) How can cervical cancer rates be lowered in countries where the rates are
still high?
Ideally, increased use of Pap tests, combined with vaccination, would be
used. Realistically, vaccination may provide an easier method for
effectively lowering cervical cancer rates in areas where medical care is
lacking and/or difficult to implement.
(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?
For cancers with genetic predispositions, the most effective early
screening may be genetic testing and analyses of family histories.
For cancers with strong environmental components, early-screening
programs for those with risk factors, avoidance of risk factors, and similar
approaches may be effective.
For cancers associated with viruses, vaccinations may be effective,
combined with screening programs (especially for those cancers known to
be affected with a particular virus).
Students may come up with specific approaches for specific forms of
cancer discussed in the text.
48. If you were assigned to study a new form of cancer, 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?
Initially, it may be helpful to look at family histories to see whether the
disease is more common among relatives than in the general population. If
there is evidence that the disease runs in families, then more timeconsuming molecular genetic analyses can be used to attempt to identify
specific genes that may be associated with the disease. Specific molecular
techniques can also be discussed.
It may also be helpful to look at incidences of the disease in different
populations, such as migrant populations, to see whether populations with
Cancer Genetics
similar genetic profiles show different disease profiles in different
Surveys may be useful to attempt to determine whether any suspected
environmental factors differ significantly between groups being studied.
49. The development of colon cancer is relatively well understood. Describe the
steps of the development of colon cancer, including any genetic components.
There can be a genetic basis to colon cancer, but most cases are sporadic.
Familial adenomatous polyposis coli is an example of a hereditary colon
In the most common sequence, there are three major stages.
(1) A mutation inactivates the APC gene early on. This increases the rate of
cell division and causes polyps to form.
(2) Later, mutations develop in the ras oncogene. This leads to a continual
stimulatory signal for cell division (the ras proto-oncogene is involved in
signal transduction).
(3) Mutations in p53 occur much later. This results in accumulations of
mutations because cell division occurs when cells are already damaged.
p53 normally prevents division of genetically damaged cells and aids in
chromosome segregation.
50. Describe an example in which environmental factors interact with a genotype
to produce cancer.
Although lung cancer is clearly associated with smoking, recent genomewide association studies show that variation at several genes predisposes
some people to smoking-induced lung cancer, either by increasing their
likelihood of becoming addicted to smoking or by affecting metabolism of
carcinogens in cigarette smoke.
Another example is skin cancer in individuals who are genetically defective
in DNA repair pathways, which depends on DNA damage from exposure to
sunlight. Such individuals likely would be susceptible to a variety of
cancers that result from exposure to carcinogens that cause damage to
51. Explain how DNA sequencing studies can aid in our understanding of cancer
DNA sequencing technology has been used to completely sequence the
DNA of tumor cells at various stages of cancer development. Tumor DNA
sequences can be compared to DNA of normal cells to identify genetic
Chapter 23
changes that might contribute to cancer formation. Also, comparison of
tumor DNA at various stages of cancer development (e.g., metastasized vs.
not metastasized) can allow scientists to better understand mechanisms of
tumor evolution and cancer development.
52. A headline in the June 12, 2009, issue of ScienceDaily 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 a microRNA might stop cancer in its tracks.
MicroRNAs are small RNAs that pair with complementary sequences on
mRNA and degrade the RNA or otherwise inhibit its translation and thereby
reduce or eliminate expression of the corresponding gene product. Many
tumor cells exhibit widespread reduction in the expression of many
microRNAs. The evidence suggests that these microRNAs are expressed
at high levels in normal cells and probably inhibit the expression of
oncogenes. Genetic changes that reduce the abundance of microRNAs
can release expression of oncogenes and bring about tumor formation and
progression. Presumably the microRNA used in the study enters the tumor
cells and shuts down expression of one or more oncogenes and stops the
progression of the cancer.
53. 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?
Driver mutations contribute directly to the development of cancer, while
passenger mutations “go along for the ride.” Passenger mutations might
result from genetic instability in cancer cells, but they do not contribute to
the cancer process. “Knock-in” technology is used to replace a section of
a normal gene with a mutant sequence. Candidate mutations identified in a
cancer genome sequencing project could be introduced into noncancerous
cells by knock-in and assessed for their ability to cause the cells to
become cancerous. Those mutations that cause normal cells to become
cancerous would be identified as driver mutations. However, some driver
mutations might be missed if they depend on the presence of other
“codriver” mutations to contribute to the cancer process.