Ch 22 Genetics Cancer

Which is the correct order of events in the normal pathway by which growth factors stimulate cell division (start at the top)?

1. EGF binds to receptor 2. Binding results in activation of intracellular signaling pathway 3. Pathway, signal cascade, leads to change in gene transcription. 4. Gene products function to promote progression through the cell cycle

Which of the following accurately describes the genetic change(s) leading to malignancy?

A series of successive gene changes occurs, involving oncogene activation and inactivation of tumor-suppressor genes.

Which of the following can lead to an association between epigenetic changes and human disease?

An environmental agent that causes the disease also causes certain types of epigenetic changes unrelated to the disease. The disease symptoms arise first and then they cause subsequent epigenetic changes to happen. The epigenetic changes directly contribute to the disease symptoms.

To stimulate the growth of epidermal cells, such as skin cells, which event would occur first?

An epidermal growth factor, EGF, binds to a receptor on the surface of a skin cell.

The loss of a chromosome carrying a tumor-suppressor gene is an example of a way of losing the function of this gene through

Aneuploidy

Tumor-suppressor protein p53 inhibits the division of cells with damaged DNA by promoting which process(es)?

Apoptosis, DNA repair and inhibition of cell cycle progression

Which environmental agents have been associated with epigenetic changes related to cancer development?

Arsenic Cadmium in tobacco smoke Nickel Benzene in tobacco smoke

Inherited breast cancer is associated with inactivation of the BRCA1 allele. Suppose a woman whose genotype is BRCA1+ BRCA1- develops breast cancer. What is the genotype of her breast cancer cells?

BRCA1- BRCA1-

During the initial stage of cancer development, cells with a precancerous genetic change form a(n)

Benign growth

In what disease do genetic changes lead to uncontrolled cell growth?

Cancer

Chemicals in the environment that cause cancer are called

Carcinogens

Which of the following are detected when visualizing the chromosomes of cancer cells by microscopy?

Changes in the number of chromosomes Abnormalities in chromosome structure

Which change from proto-oncogene to oncogene occurred by chromosomal translocation?

Creation of a new transcription factor through the fusion of chromosomal segments from two different chromosomes

Which mechanism accounts for the conversion of c-myc to an oncogene for lymphomas occurring in birds?

DNA from the avian leukosis virus integrates next to the chromosomal c-myc gene and increases its level of transcription.

Clinical improvement in leukemia patients has been observed when providing drugs that inhibit the enzyme

DNA methyltransferase.

A cell is more likely to accumulate cancer-causing mutations if it loses the activity of

DNA repair enzymes; A cell that loses the function of a DNA repair enzyme is more likely to accumulate cancer-causing mutations.

According to the accompanying pedigree, what is the inheritance pattern of the allele for inherited breast cancer, BRCA1?

Dominant inheritance with incomplete penetrance

Which genetic material is carried by viruses that cause cancer?

Either RNA of retroviruses or DNA of DNA viruses

A cancer-causing change occurs when a tumor-suppressor gene is

Inactivated

Which change from proto-oncogene to oncogene occurred by gene amplification?

Increase in the number of copies of the gene for a growth factor receptor in breast cancer cells

A series of genetic changes, involving oncogene activation and tumor-suppressor gene inactivation, leads to

Malignancy

Which type of growth has cells that can invade other tissues and migrate to other areas of the body to form secondary tumors?

Malignant growth

The ability of cancer cells to migrate to other parts of the body where they can cause secondary tumors is referred to as

Metastasis

Mutations in DNA ___, an enzyme catalyzing changes that inactivate genes, have been associated with the development of acute myeloid leukemia.

Methyltransferase

The proto-oncogene raf codes for an enzyme that participates in a signal transduction pathway promoting cell division. Changing the amino acid valine to glutamic acid at position 599 in the RAF enzyme leads to a type of skin cancer called melanoma. This change from proto-oncogene to oncogene occurred as a result of

Missense mutation

Genome maintenance includes cellular mechanisms that prevent which two processes?

Mutation; Division or survival of mutant cells

Depending upon the location of nucleosomes after chromatin remodeling, these changes may lead to cancer due to an increase in the expression of ___ or an inhibition of the expression of ___ ___ genes

Oncogenes; tumor suppressor

For the inherited tendency to develop retinoblastoma in the first few years of life, which correctly describes inactivation of the rb tumor-suppressor alleles by the "two-hit" model?

One allele is inactivated prior to birth, the other becomes inactivated early in life.

Which event activates progression through the cell cycle?

Phosphorylation of Rb protein so that it no longer binds to transcription factor E2F.

In which two ways have tumor-suppressor genes been shown to act within cells?

Regulating the rate of cell division and maintaining genomic integrity

Which change from proto-oncogene to oncogene occurred by a missense mutation?

Substitution of valine for glycine at position 12 in the amino acid sequence of the rasH protein

Which outcome is consistent with the genetic change that occurs when a cell loses both members of a homologous chromosome pair?

The loss of tumor-suppressor genes on these chromosomes causes the cell to grow uncontrollably.

Cancer can result from inactivation of which type of gene?

Tumor-suppressor gene

What is the normal role of Rb protein during the process of cell division?

Unphosphorylated Rb protein prevents progress through the cell cycle by binding to transcription factor E2F.

How can integration of viral DNA into a host chromosome convert a proto-oncogene into an oncogene?

Viral promoter or enhancer sequences increase transcription of a nearby proto-oncogene.

A benign tumor is

a localized growth with a precancerous genetic change.

Cancer cells often show

abnormalities in chromosome number and structure.

Checkpoint proteins regulate the levels of

activated cyclin-CDK complexes.

Viruses that are effective at causing cancer in both laboratory animals and cells in tissue culture are called

acutely transforming viruses.

A carcinogen is

an environmental agent that causes cancer.

A series of events leading to programmed cell death is called ___.

apoptosis

The medication Gleevec has been effective against chronic myelogenous leukemia due to its ability to

bind to the active site of the ABL enzyme, reducing its activity.

The medication Gleevec reduces the activity of the tyrosine kinase ABL in white blood cells of chronic myelogenous leukemia patients by

binding to the active site of the ABL enzyme.

In the development of retinoblastoma, a retinal cell is more likely to divide if

both copies of the RB gene are inactivated.

Viruses that cause cancer are

both retroviruses and DNA viruses.

Apoptosis relies on the digestion of cellular proteins by enzymes called

caspases

A protein that stops progression through the cell cycle if the cell has DNA or chromosomal irregularities is called a(n)

checkpoint protein.

The formation of activated cyclin-CDK complexes is regulated by

checkpoint proteins

In cancer biology, transformation is the process of

converting a normal cell into a malignant cell.

If a comparison of two variables shows that they increase together, a positive ___ is demonstrated and, if the results are statistically significant, a true ___ between the variables is suggested.

correlation; association

Two types of proteins that form activated complexes to promote a cell's progress through the cell cycle are

cyclins and cyclin-dependent protein kinases.

Caspases are enzymes that

digest cellular proteins during apoptosis.

Epigenetic changes associated with human disease can occur ___ when the changes contribute to the disease symptoms or ___ when a third factor, such as an environmental agent, causes changes that do not contribute to the symptoms.

directly; indirect

Acutely transforming viruses

efficiently transform cells in culture. induce tumors rapidly in animals.

Tobacco products have been known to promote cancer-causing mutations but recent studies also show that these environmental agents can also cause ___ changes that can lead to cancer.

epigenetic

Mutations in the genes for enzymes that catalyze the additions or removals of ___, ___, or ___ on histones have been implicated in the development of cancer.

ethyl, methyl, phosphate

An oncogene is typically formed by a _______ mutation in a normal gene called a(n) _______.

gain-of-function ; proto-oncogene

A signaling molecule that can promote division of cells throughout the body of a multicellular organism is called a(n)

growth factor.

A cancer cell is a cell that

has accumulated genetic changes that allow it to grow uncontrollably.

A malignant tumor

has cells with cancerous mutations leading to uncontrolled growth. can invade nearby healthy tissue. can form secondary tumors after spreading to other locations.

An individual who is heterozygous for a defect in a tumor-suppressor gene

has inherited an increased susceptibility to develop cancer.

Most individuals who are born with an inherited form of cancer susceptibility are

heterozygous for a defect in a tumor-suppressor gene.

The accompanying pedigree shows that breast cancer is inherited with a dominant allele showing incomplete penetrance. This is because

heterozygous individuals show the tendency to develop breast cancer.

The development of cancer could be promoted if an abnormally ___ level of methylation occurred at CpG islands near the start site of a tumor-suppressor gene.

high

Which of the following is an epigenetic change that would likely lead to cancer?

hypermethylation inhibits the expression of a tumor suppressor gene

Covalent modifications of histones can promote cancer development by

increasing the expression of oncogenes. inhibiting the expression of tumor-suppressor genes.

To prevent cells with damaged DNA from dividing, the tumor-suppressor protein p53 can

initiate apoptosis. activate genes involved with DNA repair. stimulate the expression of the p21 gene to inhibit the G1 to S transition of the cell cycle.

A cell that loses the function of a DNA repair enzyme

is more likely to accumulate cancer-causing mutations.

Ras protein is in its active form when

it is bound to GTP.

Loss of heterozygosity is

loss of function of a normal allele when the other allele was already inactivated.

The loss of function of a normal allele when the other allele for that gene was already inactivated is called

loss of heterozygosity.

Tumor-suppressor genes normally act to

maintain genome integrity. negatively regulate cell division.

Cellular mechanisms that prevent mutations from occurring and/or prevent mutant cells from dividing or surviving are referred to as genome

maintenance

Cancer cells can migrate to other parts of the body and cause secondary tumors. This property is called

metastasis

To potentially reverse the inactivation of tumor-suppressor genes, researchers are developing potential cancer treatments that involve inhibition of the enzyme DNA ___.

methyltransferase

A checkpoint protein

monitors the state of the cell and stops progression through the cell cycle if damage is detected.

If the function of Rb protein is lost in a retinal cell, that cell is

more likely to divide

An oncogene is formed when a proto-oncogene gains a

mutation that causes its expression to be abnormally active.

Cancer could develop if chromatin remodeling established a nucleosome-free region on the promoter for a(n)

oncogene

By the action of tumor suppressor protein p53, which gene shows increased expression to slow progress through the cell cycle and provide time for DNA repair?

p21

If an increase in DNA methylation of a gene is associated with an increase in severity of a specific disease, these two variables show a(n)

positive correlation.

A tumor-suppressor gene codes for a protein that normally

prevents cancerous growth.

Apoptosis refers to a controlled series of events called

programmed cell death.

At the cellular level, breast cancer development is

recessive because the cell must become homozygous for a loss-of-function allele.

The binding of a specific cyclin and cyclin-dependent protein kinase forms an activated protein complex that

regulates a cell's progress through the cell cycle.

A cancer-causing mutation in the ras gene leads to an altered Ras protein that

remains bound to GTP.

A growth factor is a

signaling molecule that can stimulate cells throughout the organism's body to divide.

In one study of inherited breast cancer, there was a substitution of glycine for cysteine at position 64 in the tumor-suppressor protein BRCA1. This mutation led to cancer development because

the activity of the tumor-suppressor protein was reduced, so it was no longer able to inhibit cell growth.

Chronic myelogenous leukemia is due to production and overexpression of a BCR/ABL fusion protein caused by

translocation of the portion of chromosome 9 carrying the abl gene to the area of chromosome 22 with the bcr gene.

A gene that codes for a protein that prevents cancerous growth is a(n)

tumor-suppressor gene.

For the non-inherited development of retinoblastoma, which correctly describes inactivation of the rb tumor-suppressor alleles by the "two-hit" model?

The person is born with two active copies of the rb allele; separate mutation events are required to inactivate each of these alleles.

Suppose a translocation occurs so that a portion of one chromosome is joined to another non-homologous chromosome. Which situation would cause the cell to grow uncontrollably as a result?

The sequence arrangement in the newly-fused chromosome leads to overactive expression of a proto-oncogene.

Cancer cells may carry gain-of-function mutations that increase the activity of an oncogene. In which of the following ways could the expression of the protein encoded by the oncogene be altered by this type of mutation?

The structure of the protein is altered so that it is overly active. The amount of protein produced from the oncogene is significantly increased. The protein is expressed in a cell type where it is not normally found.

Ewing's sarcoma is a cancer of the bone and soft tissues where a new transcription factor is produced from the fusion of the coding regions of two different proteins. The ews gene of chromosome 22 is joined to the fli1 gene of chromosome 11. Neither the ews nor the fli1 gene individually causes cancer. This change from proto-oncogene to oncogene occurred as a result of

chromosomal translocation.

The ERBB2 receptor normally plays a role in promoting cell division. Cells from many breast cancer patients show an increase in the number of ERBB2 receptors available on the plasma membrane. The type of mutation that contributed to cancer development in these cases would be called a ______-of-function mutation in a(n) ______.

gain; oncogene

The proto-oncogene cdk4 encodes an enzyme that helps control the entry of cells into the S phase of the cell cycle. Some cases of sarcoma result from an oncogenic conversion of cdk4 where an increased number of cdk4 copies have been detected at the original gene locus. This change from proto-oncogene to oncogene occurred as a result of

gene amplification.

Li-Fraumeni syndrome is an inherited tendency toward cancer development that relates to changes in the tumor-suppressor protein p53. A common change is the substitution of tryptophan for arginine at position 248 in the amino acid sequence. This is an example of inactivating a tumor-suppressor gene through

mutation

A gene that promotes cancer is called a(n)

oncogene

A mutant gene that is overexpressed and contributes to the formation of cancer is termed a(n)

oncogene

Which gene acts to prevent accumulation of mutations by activating DNA repair genes in cells with damaged DNA?

p53

Which gene plays a significant role in detecting DNA damage in a cell?

p53

Which gene stimulates the expression of p21 to slow progress through the cell cycle when DNA damage is detected?

p53

For chronic myelogenous leukemia, a chromosomal translocation leads to

production of a BCR/ABL fusion protein that promotes division of white blood cells.

A normal, nonmutated gene that has the potential to become an oncogene is called a(n) ___-oncogene.

proto

A normal gene that when mutated becomes an oncogene is called a(n)

proto-oncogene.

Aneuploidy is a mechanism for losing the function of a tumor-suppressor protein because

the chromosome carrying the tumor-suppressor gene can be lost from the cell.