Ch 16 - Cancer Genetics

Select the events that are a consequence of activating mutations in the ras gene.

- Abnormally rapid cell growth and proliferation is induced. - Specific transcription factors are activated by phosphorylation. - The ras proto-oncogene is converted into an oncogene.

Which of the mutations described have the potential to cause cancer?

- a loss-of-function mutation in a tumor suppressor gene - a gain-of-function mutation in a proto-oncogene

Select the statements that accurately describe different ways that translocations could lead to cancer.

-Gene for a protein that regulates the cell cycle is placed next to the regulatory sequence of a different gene. The gene is now expressed at inappropriate times -Translocation breaks up the sequence of a gene for a tumor-suppress or protein. The resulting protein cannot function properly -New sequence is added to a proto-oncogene. The modifed gene now produces a new protein that increases the rate of cell division

The figure shows the karyogram of a human cancer cell. Select the statements that the karyogram supports.

-Part of chromosome 6 has been translocated to the X chromosome -Chromosome 5 has been duplicated

Place the event that control the progression of cells through the G1/S checkpoint of the cell cycle in order.

1. Cyclins D and E bind CDK proteins. 2. Cyclin‑CDK complexes phosphorylate RB proteins. 3. Inactivated RB releases active E2F protein. 4. E2F transcribes genes required for DNA replication.Last event

Which of these genes often suffers a mutation very early in the progression of colon cancer? NF1 APC p53 RB

APC Among the earliest steps is a mutation that inactivates the APC gene; this mutation increases the rate of cell division, leading to polyp formation.

Which statement explains why colon cancer is an example of clonal evolution? Colon cancer has no known genetic cause. Mutations in one gene cause colon cancer. Colon cancer develops due to sequential mutation of multiple genes. Colon cancer is not treatable at any stage of the disease.

Colon cancer develops due to sequential mutation of multiple genes. Colon cancers develop by acquiring sequential mutations that increase the severity of the cancer, as defined by clonal evolution.

Colon cancer is caused by the accumulation of multiple gene mutations that result in uncontrolled cell division and growth. Arrange the steps of colon cancer progression.

Colon tissue is initially healthy. Inactivating APC mutations give rise to benign polyps. Intermediate adenomas are formed by mutations in ras. Late adenomas are formed by the inactivation of DCC and Smad4. Adenocarcinomas are generated by mutations in p53. Adenocarcinomas become metastic by unknown mutations Colon cancer invades neighboring tissues

Assuming that the rest of the genome is normal, cells with an inactivating mutation in one copy of a tumor-suppressor gene with the second copy of the gene still wild-type are most likely to _____. disregard cell-cycle checkpoints and divide inappropriately stop dividing when they normally should divide begin to overproliferate and begin a progression toward cancer continue normal divisions for this cell type

continue normal divisions for this cell type The cell is heterozygous for the mutation, which is usually recessive, so there will be no abnormal effect.

What is NOT an example of an environmental factor that can contribute to cancer? tobacco family pedigree benzene UV radiation

family pedigree Pedigrees are used to analyze the pattern of inheritance of a particular trait throughout a family.

Why do mutations in DNA repair genes typically lead to aggressive and accelerated cancer progression? DNA repair genes have a higher rate of mutation than other genes. DNA repair genes play an important role in cell proliferation. DNA repair genes repair mutations in DNA, so if they themselves are mutated, a cell may have a higher mutation rate in genes that play a role in cancer. DNA repair genes get translated into proteins that cause mutations in other parts of the cell.

DNA repair genes repair mutations in DNA, so if they themselves are mutated, a cell may have a higher mutation rate in genes that play a role in cancer. A deficiency in the DNA repair mechanism may allow harmful mutations to persist, which can lead to the onset of cancer.

Some cancers have been treated with drugs that demethylate DNA. Explain how these drugs might work. Do you think the cancer-causing genes that respond to the demethylation are likely to be oncogenes or tumor-suppressor genes?

Demethylation would transcriptionally activate any genes that had been silenced by methylation and would have variable effects depending on whether tumor suppressors or oncogenes or both are activated.

Assume that a provirus inserts just upstream of a tumor-suppressor gene with a strong viral promoter. Would this insertion be likely to cause cancer? Why or why not? No, since tumor-suppressor genes are resistant to viral infection. No, the expression of tumor-suppressor genes decreases the likelihood of cancer. Yes, the provirus insert will replace the tumor-suppressor gene. Yes, the increased expression of a tumor-suppressor gene increases the likelihood of cancer.

No, the expression of tumor-suppressor genes decreases the likelihood of cancer. The viral promoter will increase the inhibition of tumor formation.

Which of the given factors increase the risk of developing cancer?

Obesity, over-consumption of alcohol, UV light exposure, less than 2 hrs of physical exercise a wk, smoking tobacco, diet rich in animal fat and processed meat Only a small percentage of cancers are caused solely by genetically inherited mutations. Most cancers are the result of exposure to environmental factors that have damaged the DNA in specific cells. Avoiding these environmental risk factors decreases the risk of developing cancer.

Which of these statements does NOT provide evidence for cancer as a genetic disease? Ionizing radiation and chemicals that cause mutations also cause cancer. Some cancers are consistently associated with particular chromosome abnormalities. Some cancers are found in patients with no family history of cancer. Some specific types of cancers tend to run in families.

Some cancers are found in patients with no family history of cancer. A lack of family history would NOT support the idea of cancer as a genetic disease.

Suppose Alia recently learned that she inherited a mutant BRCA1 allele from her mother, who had breast cancer. BRCA1 is a tumor suppressor gene that is related to breast cancer. Why would Alia be at higher risk for getting breast cancer at an earlier age than her sister, Tiffany, who inherited a normal BRCA1 allele from their mother?

Someone with one mutant allele in a tumor suppressor gene only requires a mutation in the one remaining normal allele for tumors to form.

Both genes and environment factors contribute to cancer. The table shows that prostate cancer is 30 times more common among Caucasians from Utah as among Chinese from Shanghai. Briefly outline how to determine if these differences in the incidence of prostate cancer are due to differences in the genetic makeup of the two populations or to differences in their environment.

if the differences are due to genetic makeup only, then people who migrated from Utah or Shanghai to elsewhere would have a similar cancer rate as people who stayed in Utah or Shangai If the differences are due to the environment only, then people who migrated from Utah or Shanghai would have rates of cancer determined by their location and not by their place of origin

In a common pathway by which colon cells become cancerous, what is the correct order of mutations in the following genes: p53, ras, and APC? loss of APC, activation of ras, loss of p53 activation of p53, activation of ras, activation of APC loss of ras, activation of APC, loss of p53 loss of APC, activation of p53, loss of ras

loss of APC, activation of ras, loss of p53 First, the loss of normal tumor-suppressor gene APC occurs, followed by activation of the oncogene ras, then finally the loss of tumor-suppressor gene p53.

Which of these describes a mechanism by which a virus can contribute to the onset of cancer? preventing the cell from passing through the G1/S checkpoint via the retinoblastoma protein, which binds to a transcription factor, called E2F, and keeps the cell inactive. bringing together sequences from two different genes, generating a fusion protein that stimulates some aspect of the cancer process Bringing together sequences from two different genes, generating a fusion protein that stimulates some aspect of the cancer process. mutating and rearranging host genes, converting proto-oncogenes into oncogenes, or altering the expression of host genes

mutating and rearranging host genes, converting proto-oncogenes into oncogenes, or altering the expression of host genes If the provirus inserts near a proto-oncogene, viral promoters can stimulate high levels of expression of the proto-oncogene, leading to cell proliferation.

Retroviruses can cause cancer by ____ proto-oncogenes or _____ near proto-oncogenes. deleting; inserting strong promoters mutating or rearranging; inserting strong promoters deleting; inserting suppressors mutating or rearranging; inserting suppressors

mutating or rearranging; inserting strong promoters Retroviruses sometimes cause cancer by mutating and rearranging host genes, converting proto-oncogenes into oncogenes. Another way in which viruses can contribute to cancer is by altering the expression of host genes.

Two chromosomes in a cell undergo reciprocal translocation such that a proto-oncogene ends up next to a strong promoter. Which result is most likely? overexpression of the proto-oncogene, resulting in cancer development no expression of the proto-oncogene, and normal cell divisions decreased expression of the proto-oncogene, resulting in normal cell divisions overexpression of the proto-oncogene, preventing cancer development

overexpression of the proto-oncogene, resulting in cancer development Regulation by a strong promoter will result in strong expression of the proto-oncogene.

What is typically more detrimental to an organism? small primary tumor small secondary tumor no tumors large primary tumor

small secondary tumor In the development of many cancers, the primary tumor gives rise to cells that spread to distant sites, producing secondary tumors, which is called metastasis.

In 1909, Peyton Rous determined that a sarcoma growing on a chicken's breast was caused by the retrovirus Rous sarcoma. Later, the first oncogene, src, was isolated from this virus and found to contribute to cancer formation. Where did src come from? a bacterial genome the retroviral genome the human genome the genome of the virus' host, likely a chicken

the genome of the virus' host, likely a chicken When a virus infects a cell, a proto-oncogene may become incorporated into the viral genome through recombination. Within the viral genome, the proto-oncogene may mutate to an oncogene that, when inserted back into a host cell, causes rapid cell division and cancer.

Loss of heterozygosity, which often results in progression toward cancer, refers to which of these? the gain of a wild-type allele for a tumor-suppressor gene when the cell is homozygous for a recessive mutation at this locus a mutation in a tumor-suppressor gene when the cell is heterozygous at another tumor-suppressor gene locus the appearance of an abnormal trait in an individual cell or organism that is heterozygous for that trait the loss of the tumor-suppressor gene wild-type allele when the cell is heterozygous for a recessive allele

the loss of the tumor-suppressor gene wild-type allele when the cell is heterozygous for a recessive allele Inactivation of the remaining wild-type allele of a heterozygote is referred to as the loss of heterozygosity.

The Philadelphia chromosome is: an artificial chromosome originally produced in Philadelphia at the University of Pennsylvania. the result of a translocation between the long arms of chromosomes 9 and 22 that produces a hybrid fusion gene. a chromosome 22 with a large deletion in the long arm. an inversion

the result of a translocation between the long arms of chromosomes 9 and 22 that produces a hybrid fusion gene. The Philadelphia chromosome is a shortened chromosome 22, which is created as a result of this translocation.

A woman has the inherited form of retinoblastoma (RB). Her husband does not have RB, and they have monozygotic (identical twins) twin girls. One girl got RB before the age of 5, and her twin avoided RB throughout her entire childhood. How is this possible? Both girls inherited the RB mutation, but in one girl, the inherited normal copy of the RB gene suffered a somatic mutation that led to RB, and the other girl did not suffer a somatic mutation in her normal copy of the gene. One girl inherited the RB mutation from the mother and the other girl didn't. Both girls inherited the RB mutation, but in the girl that did not suffer from RB, a back mutation occurred in the mutated RB gene somatically that resulted in the restoration of the wild-type allele. Both girls inherited the RB mutation but, in one girl, a defect occurred in a mismatch repair gene which led to a number of somatic mutations in several tumor-suppre

Both girls inherited the RB mutation, but in one girl, the inherited normal copy of the RB gene suffered a somatic mutation that led to RB, and the other girl did not suffer a somatic mutation in her normal copy of the gene. Both girls inherited the RB mutation, but one suffered a somatic mutation in the second copy of the gene and acquired RB while the other girl did not.

Cancer cells divide uncontrollably, evading the signals that regulate the cell cycle. Classify the characteristics as those of cancer cells or normal cells.

Cancel cells: Have abnormal number of chromosomes Enter new tissues and grow there Do not respond to external cell signals Contain unusually high number of gene mutations Do not stop dividing when crowded Normal cells: Differentiate into specialized cells Undergo apoptosis if genome is damaged Adhere to neighboring cells within a tissue Self-destruct if nucleus is abnormal

How can cancer be a genetic disease but rarely inherited? Cancer is always caused by spontaneous mutations in germ line cells, so it cannot be inherited. Cancer is caused by environmentally caused mutations only; thus it cannot be inherited. Cancer is caused by post-translational modifications of proteins, which are not inherited. Cancer is caused by multiple mutations in genes, but it is rarely inherited because the mutations needed typically happen in somatic cells over an individual's lifetime.

Cancer is caused by multiple mutations in genes, but it is rarely inherited because the mutations needed typically happen in somatic cells over an individual's lifetime. Since the occurrences of mutations are in somatic cells, it is seldom seen passed down from generation to generation.

Cancer is fundamentally a genetic disease. Which statement does NOT correctly describe the genetic nature of cancer? Cancer is only caused by mutations we inherit from our parents. Some environmental agents may increase mutations that lead to cancer. More than 350 genes are linked to cancer in humans. Mutations in DNA repair genes are linked to cancers.

Cancer is only caused by mutations we inherit from our parents. Cancer can also be caused by environmental factors such as lifestyle choice and exposure to mutagens.

The diagram shows the relative activity of a proton-oncogene and a tumor suppressor gene in a normal cell, as well as the activity in four other cells. Which of these cells would be expected to be cancer cells?

Cell B & cell C

How does the environment influence cancer development if cancer is a genetic disease? Environmental factors can change the rate at which somatic mutations accumulate. Cancers are very unlikely to develop in an individual with a healthy diet because cancer cells will not be able to divide. Cancer cells do not grow in certain climates. Environmental factors determine which genes you inherit from your parents.

Environmental factors can change the rate at which somatic mutations accumulate. The role of environmental factors in cancer is suggested by differences in the incidence of specific cancers throughout the world.

Which of these puts the physical changes associated with colon cancer in the CORRECT order? I: A benign, precancerous tumor grows. II: The cancer metastasizes (spreads to other tissue through the bloodstream). III: A polyp (small growth) forms on the colon wall. IV: An adenoma (benign tumor) grows. V: A carcinoma (malignant tumor) develops. III, I, IV, V, II I, II, III, IV, V III, V, IV, I, II II, IV, I, III, V

III, I, IV, V, II This is the correct order for the sequence of physical changes associated with colon cancer. Polyp forms in the colon wall - Benign, precancerous tumor grows - Adenoma (benign tumor) grows - Carcinoma (malignant tumor) develops - Cancer metastasizes (spreads to other tissues through the bloodstream)

A rare hereditary liver cancer is observed in several members of a family. The inheritance of this cancer is represented in the given pedigree. For each individual in generation III, DNA was isolated from normal tissue as well as from tumors of the affected individuals. A gene that is closely associated with this cancer was analyzed by PCR, and the resulting data is shown in the given gel. Based on the pedigree and DNA gel, which unaffected individual in generation III is most likely to acquire this form of liver cancer?

Individual 15

Chronic myelogenous leukemia often results from a reciprocal translocation between chromosomes 9 and 22. How does this event lead to cancer? It moves the RAS gene to a genomic location, where its expression level is too low for it to function normally as a tumor-suppressor gene. It leads to an increased mutation rate throughout the genome, and some of these mutations lead to inactivated tumor suppressor genes. It produces a fusion gene consisting of parts of the c-ABL and BCR genes, and this fusion gene acquires oncogenic activity. It moves the c-MYC gene to a genomic location, where it comes under control of a regulatory region that enhances its expression level.

It produces a fusion gene consisting of parts of the c-ABL and BCR genes, and this fusion gene acquires new oncogenic activity.

If a person is exposed to a chemical mutagen that damages their DNA in such a way as to predispose them to cancer, will this person pass this cancer predisposition down to their children? No, cancer is not an inherited disease. Yes, the chemical will remain in the body and get passed down to the person's children, where it will mutate their DNA as well. Maybe, if the cancer-causing mutations happen in germ line cells, there is a chance that the cancer could be passed down to their children. Yes, since the mutagen mutated this person's DNA, it will be passed down to their children.

Maybe, if the cancer-causing mutations happen in germ line cells, there is a chance that the cancer could be passed down to their children. The defect can occur in either somatic or sex cells.

Which of these statements suggests that environment influences cancer rates? Some families have a predisposition for cancer. Most cancers are caused by mutations in several different genes. Migrating populations may take on the cancer rates of their host country. Not everyone who smokes cigarettes develops lung cancer.

Migrating populations may take on the cancer rates of their host country. Migrating populations will be affected by the environment of their host country, while still having a genetic composition more similar to people of their home country.

How does cancer differ from most other genetic disorders?

Most genetic disorders are inherited through germ cells from parents. Most cancers are, to some extent, the result of mutations in somatic cells that occur during an organism's lifetime.

Match each definition with the corresponding term concerning genes involved in tumor formation.

Proto-oncogenes: a normal gene that drives inappropriate cell division if abnormal over-expressed// a gene regulating cell division that can be mutated into tumorigenic form.

Why are retroviruses, in particular, associated with cancer? Retroviruses insert their genome into the host genome, which could cause disruptions or expression changes in important genes. Retroviruses protect themselves from the host immune system by causing their host cell to grow and divide. A retrovirus needs a host cell to replicate; part of the replication machinery is to form a tissue-like "command center" that then becomes a tumor. Retroviruses cause the host cell to lyse after viral DNA replication is complete, triggering the growth and division of the surrounding cells.

Retroviruses insert their genome into the host genome, which could cause disruptions or expression changes in important genes. Retroviruses sometimes cause cancer by mutating and rearranging host genes, converting proto-oncogenes into oncogenes.

All of these are mechanisms involved in chromosome mutations and are associated with cancer EXCEPT which one? The chromosome breaks that accompany these mutations can lie within tumor-suppressor genes, disrupting their function and leading to cell proliferation. The transfer of a potential cancer-causing gene to a location where it is activated by different regulatory sequences. Bringing together sequences from two different genes, generating a fusion protein that stimulates some aspect of the cancer process. The cell is prevented from passing through the G1/S checkpoint by the retinoblastoma protein, which binds to a transcription factor, called E2F, and keeps it inactive.

The cell is prevented from passing through the G1/S checkpoint by the retinoblastoma protein, which binds to a transcription factor, called E2F, and keeps it inactive. This mechanism only affects the cell cycle instead of altering the structure of a chromosome.

Chronic myelogenous leukemia is often associated with which of these events? a mutation in the APC gene a deletion a translocation an inversion

a translocation Most people with chronic myelogenous leukemia have a reciprocal translocation between the long arm of chromosome 22 and the tip of the long arm of chromosome 9.

The pedigree shows a family in which several family members have a rate hereditary liver cancer. DNA was isolated from normal tissue of each individual in generation III. DNA was also isolated from liver tumors of the affected individuals. The genomic region closely associated with this cancer was analyzed by PCR, and the data is shown in the gel. Based on the pedigree and DNA gel, select the correct statement about the gene associated with this cancer.

The gene is a tumor suppressor gene because cells that contain both the normal and cancer‑associated alleles are normal.

A genetic counselor determines that patients with a deletion in a particular region of a chromosome are more likely to develop cancer than other people. Is the gene responsible for the increased risk of cancer a tumor suppressor or a proto-oncogene?

The gene is a tumor suppressor, because tumor suppressor genes induce apoptosis in abnormal cells.

If the environment played a large part in the development of lip cancer, how would you expect the incidence rate to change in a large group of Canadians who moved to Brazil? Examples of geographic variation in the incidence of cancer [see image] The incidence rate would decrease. The incidence rate would increase. The incidence rate would stay the same. It would be impossible to predict.

The incidence rate would decrease. The results of studies show that migrant populations typically take on the cancer incidence of their host country.

Why would mutations in parts of the mitotic spindle apparatus lead to cancer? The mitotic spindle apparatus prevents the cell membrane from rupturing and leading to cancer. The mitotic spindle apparatus ensures that chromosomes separate in mitosis, so if it is mutated, you could end up with two daughter cells with different numbers of chromosomes. The mitotic spindle apparatus controls entry into the cell cycle, so the cell would continuously divide. The mitotic spindle apparatus has a high mutation rate and is therefore an early target of cancer.

The mitotic spindle apparatus ensures that chromosomes separate in mitosis, so if it is mutated, you could end up with two daughter cells with different numbers of chromosomes.

Refer to Table 16.2. If the environment did NOT play a role in cancer development, how would the rate of colon cancer in Texas compare to the rate in Minnesota? Examples of geographic variation in the incidence of cancer Type of Cancer / Location / Incidence rate Lip / Canada (Newfoundland) / 15.1 / Brazil (Fortaleza) / 1.2 Nasopharynx / Hong Kong / 30.0 / United States (Utah) / 0.5 Colon / United States (Iowa) / 30.1 / India (Mumbai) / 3.4 Lung / U.S. (New Orleans, African Americans) / 110.0 /Costa Rica / 17.8 Prostate / United States (Utah) / 70.2 / China (Shanghai) / 1.8 Bladder / United States(Connecticut, Whites) / 25.2 / Philippines (Rizal) / 2.8 All cancer / Switzerland (Basel) / 383.3 / Kuwait / 76.3 They would be different. The rate in Texas would be higher. The rate in Minnesota would be higher. They wo

They would be the same. Since environment is not a factor, it can be assumed that the mutation rate is relatively equal in the two populations

Why are tumor-suppressor genes more difficult to identify than oncogenes? You can add tumor-suppressor genes to cells and look for cancer. There are no known sequences for tumor-suppressor genes. The overexpression of tumor-suppressor genes causes cancer. To contribute to cancer, both copies of the tumor-suppressor gene must be mutated.

To contribute to cancer, both copies of the tumor-suppressor gene must be mutated. Heterozygotes are often predisposed to cancer because the inactivation or loss of the one remaining normal allele is all that is required to completely eliminate the tumor-suppressor gene product.

Which of these is an example of a chromosomal rearrangement that can lead to the onset of cancer? mutating and rearranging host genes, converting proto-oncogenes into oncogenes, or altering the expression of host genes. the cell being prevented from passing through the G1/S checkpoint by the retinoblastoma protein, which binds to a transcription factor, called E2F, and keeps it inactive. hypermethylation, which may inhibit transcription of tumor-suppressor genes, stimulating the development of cancer the transfer of a potential cancer-causing gene to a location where it is activated by different regulatory sequences

the transfer of a potential cancer-causing gene to a location where it is activated by different regulatory sequences Many people with Burkitt lymphoma possess a reciprocal translocation that operates by this mechanism.

Some cancers are consistently associated with the deletion of a particular part of a chromosome. Would the deleted region contain an oncogene or a tumor-suppressor gene? oncogene neither type of gene tumor-suppressor both oncogenes and tumor-suppressor genes

tumor-suppressor With the gene of a tumor-suppressor gene removed, a benign group of cells is then able to proliferate.