Chapter 8: Genetics of Cancer

Question 1

defined as a large number of complex diseases, up to a hundred, that behave differently
depending on the cell types from which they originate and the types of genetic alterations
that occur within each cancer type.

Answer 1

cancer

Question 2

Two fundamental properties of can cells:

Answer 2

1) abnormal cell growth and division (proliferation)

2) defects in the normal restraints that keep cells from spreading and colonizing other parts of the
body (metastasis

Question 3

types of tumor:

Answer 3

benign and malignant tumor

Question 4

a multicellular mass that grows when a cell simply loses genetic control over cell growth
and can often be removed by surgery and may cause no serious harm.

Answer 4

Benign tumor

Question 5

if cells in the tumor also have the ability to break loose, enter the bloodstream,
invade other tissues, and form secondary tumors and are often difficult to treat and may become life threatening

Answer 5

Malignant tumor

Question 6

8.2.The Role of Environmental Factors in Cancer

What is the proportion of human cancers with a hereditary or familial component, and where do most inherited cancer-susceptibility alleles occur?

Answer 6

Approximately 5 percent of human cancers have a hereditary or familial component. Most inherited cancer-susceptibility alleles occur in tumor-suppressor genes, such as p53 or RB1.

Question 7

Provide an example of a cancer type, and explain how genetic predisposition contributes to its development.

Answer 7

Colorectal cancers develop through the accumulation of mutations in several genes, leading to stepwise clonal expansion and carcinoma development. About 1 percent of colorectal cancer cases result from a genetic predisposition known as familial adenomatous polyposis (FAP).

Question 8

is a genetic predisposition to colorectal cancer characterized by the inheritance of one mutant copy of the APC (adenomatous polyposis) gene located on chromosome 5.

Answer 8

Familial Adenomatous Polyposis (FAP)

Question 9

what is the normal function of the mutated APC (adenomatous polyposis) gene product?

Answer 9

The normal function of the APC gene product is to act as a tumor suppressor, controlling growth and differentiation.

Question 10

What is the impact of a heterozygous APC mutation on the cells of the colon in individuals with FAP?

Answer 10

A heterozygous APC mutation causes the epithelial cells of the colon to partially escape cell-cycle control, leading to the formation of small clusters of cells called polyps or adenomas.

Question 12

How many colon and rectal polyps do individuals with FAP typically develop early in life?

Answer 12

Individuals with FAP typically develop hundreds to thousands of colon and rectal polyps early in life.

Question 13

In the majority of cases of familial adenomatous polyposis (FAP), what occurs in a later stage of cancer development related to the APC gene?

Answer 13

In the majority of cases, the second APC allele becomes mutant in a later stage of cancer development.

Question 14

Describe the proposed origin of colorectal cancer, including the initial stage and the type of tumor involved.

Answer 14

Colorectal cancer is thought to originate as benign tumors called adenomatous polyps. These polyps represent the initial stage of colorectal cancer development.

Question 15

What are some specific genetic changes or mutations mentioned in the context of colorectal cancer development?

Answer 15

Loss of the normal tumor-suppressor gene APC, loss of the tumor-suppressor gene p53, loss of antimetastasis gene, and activation of the oncogene ras are mentioned as genetic changes in colorectal cancer development.

Question 16

What is the percentage of human cancers associated with viruses?

Answer 16

15 percent of human cancers are associated with viruses.

Question 17

Among various risk factors for cancer, where does virus infection rank in terms of significance?

Answer 17

Virus infection is the second largest risk factor for cancer, following tobacco smoking.

Question 18

Is virus infection alone sufficient to trigger human cancers?

Answer 18

No

Question 19

what other factors are required, in addition to virus infection, to move a cell down the multistep pathway to cancer?

Answer 19

Other factors include DNA damage or the accumulation of mutations in one or more of a cell’s oncogenes and tumor-suppressor genes.

Question 20

What is the most significant carcinogen in our environment, and how does it contribute to cancer deaths?

Answer 20

Tobacco smoke is the most significant carcinogen, containing at least 60 chemicals that interact with DNA and cause mutations. Epidemiologists estimate that about 30 percent of human cancer deaths are associated with cigarette smoking.

Question 21

What is the increased risk of developing lung cancer for smokers, and how many people worldwide does lung cancer kill each year?

Answer 21

Smokers have a 20-fold increased risk of developing lung cancer. Lung cancer kills more than one million people worldwide each year.

Question 22

Which cancers are associated with the consumption of red meat and animal fat in the diet?

Answer 22

Colon, prostate, and breast cancer are associated with the consumption of red meat and animal fat in the diet.

Question 23

How does alcohol contribute to cancer, specifically in the context of the liver?

Answer 23

Alcohol may cause inflammation of the liver and contribute to liver cancer.

Question 24

Provide an example of a natural chemical carcinogen and its source.

Answer 24

Aflatoxin, a component of a mold that grows on peanuts and corn, is one of the most carcinogenic natural chemicals.

Question 25

Name a synthetic chemical carcinogen found in cigarette smoke.

Answer 25

Benzo[a]pyrene is a synthetic chemical carcinogen found in cigarette smoke.

Question 26

What types of radiation can cause DNA lesions that lead to cancer?

Answer 26

X rays and ultraviolet light can cause DNA lesions that lead to cancer.

Question 27

How does chronic inflammation due to infection contribute to DNA lesions and cancer?

Answer 27

Chronic inflammation due to infection stimulates tissue repair and cell division, resulting in DNA lesions accumulating during replication.

Question 28

found in some preserved meats,
synthetic pesticides, asbestos, benzene (used as an industrial solvent), Synthetic chemical carcinogens

Answer 28

nitrosamines

Question 29

can cause DNA lesions that lead to cancer.

Answer 29

Radiation (X rays, ultraviolet light)

Question 30

• produced from normal metabolism creates oxidative end products that can
  damage DNA, proteins, and lipids.

Answer 30

free radicals

Question 31

• stimulates tissue repair and cell division, resulting in
  DNA lesions accumulating during replication.

Answer 31

Chronic inflammation due to infection-

Question 32

What do proto-oncogenes encode?

Answer 32

Proto-oncogenes encode transcription factors, signal transduction molecules, and cell-cycle regulators.

Question 33

is a mutated or abnormally expressed proto-oncogene that causes cancer.

Answer 33

oncogene

Question 34

What is the function of tumor-suppressor genes?

Answer 34

Tumor-suppressor genes regulate cell-cycle checkpoints and initiate apoptosis.

Question 35

What happens when tumor-suppressor genes are mutated or inactivated?

Answer 35

Mutated or inactivated tumor-suppressor genes lead to abnormal responses to cell-cycle checkpoints and hinder programmed cell death, resulting in the accumulation of mutations and cancer development.

Question 36

What is the significance of the ras Proto-oncogenes in human tumors?

Answer 36

Some of the most frequently mutated genes in human tumors, mutated in 30% of all cancers.

Question 37

What is the role of Ras proteins encoded by the ras Proto-oncogenes in cell regulation?

Answer 37

Ras proteins, associated with the cell membrane,

1. regulate cell growth and division by transmitting signals from the cell membrane to the nucleus.
2. They stimulate cell division in response to external growth factors.

Question 38

How do Ras proteins normally switch between inactive and active states?

Answer 38

Ras proteins alternate between an inactive (switched off) and an active (switched on) state by binding either guanosine diphosphate (GDP) or guanosine triphosphate (GTP).

Question 39

What happens when mutations convert the ras Proto-oncogene to an oncogene?

Answer 39

prevent the Ras protein from hydrolyzing GTP to GDP. This freezing of the Ras protein in its “on” conformation constantly stimulates the cell to divide.

Question 40

What is the consequence of mutations in the ras Proto-oncogene on cell division?

Answer 40

Mutations in the ras Proto-oncogene, when converted to an oncogene, result in a constant stimulation of cell division as the Ras protein remains in its active state, unable to switch off by hydrolyzing GTP to GDP.

Question 41

• The most frequently mutated gene in human cancers— mutated in more than 50 percent
  of all cancers

Answer 41

p53 Tumor-Suppressor Gene

Question 42

What is the primary function of the p53 tumor-suppressor gene?

Answer 42

The p53 gene encodes a transcription factor that regulates the transcription of over 50 genes, involved in responses such as cell-cycle arrest, DNA repair, and apoptosis.

Question 43

How is the p53 protein regulated in normal cells, and what triggers its rapid increase in nuclear levels?

Answer 43

The p53 protein is continuously synthesized but rapidly degraded, maintaining low levels in normal cells. Cellular stress events, such as chemical damage to DNA or double-stranded breaks, trigger a rapid increase in its nuclear levels.

Question 44

In cancer cells with mutated or inactivated tumor-suppressor genes, what is the consequence regarding responses to DNA damage?

Answer 44

Cancer cells lacking functional tumor-suppressor genes are unable to respond normally to cell-cycle checkpoints or undergo programmed cell death, leading to the accumulation of mutations and cancer development.

Question 45

Define proto-oncogenes and their role in normal and cancer cells.

Answer 45

Proto-oncogenes encode products essential for normal cell functions, especially cell growth and division. In cancer cells, alterations in proto-oncogenes, such as mutations or overexpression, can lead to unregulated cell division, contributing to cancer development.

Question 46

Explain the role of the ras gene family in human tumors, and how do mutations in this family contribute to cancer?

Answer 46

The ras gene family, mutated in over 30% of human tumors, encodes signal transduction molecules regulating cell growth. Mutations convert the ras proto-oncogene to an oncogene, leading to constant stimulation of cell division.

Question 47

differentiate between proto-oncogenes and tumor-suppressor genes concerning their alterations in cancer cells.

Answer 47

Proto-oncogenes, when altered, become oncogenes with gain-of-function alterations, stimulating cell division. Tumor-suppressor genes, when mutated, result in loss-of-function alterations, affecting cell-cycle regulation and apoptosis.

Question 48

How does p53 function in normal cells to regulate the cell cycle and apoptosis?

Answer 48

In normal cells, p53 acts as a transcription factor, regulating the cell cycle at G1/S and G2/M checkpoints and inhibiting cyclin/CDK complexes. It can also induce apoptosis by activating the transcription of genes controlling this process.

Question 49

What happens in cancer cells lacking sufficient p53 regarding apoptosis?

Answer 49

In cancer cells lacking sufficient p53, the gene products controlling apoptosis are not synthesized, potentially preventing apoptosis from occurring. This contributes to the survival and proliferation of damaged cells.

Question 50

What happens to cells lacking functional p53 in response to DNA damage?

Answer 50

Cells lacking functional p53 are unable to arrest at cell-cycle checkpoints or enter apoptosis. As a result, they move unchecked through the cell cycle, regardless of the condition of the cell’s DNA.

Question 51

How does the absence of p53 impact mutation rates and the accumulation of mutations in cells?

Answer 51

Cells lacking p53 have high mutation rates and accumulate mutations that lead to cancer, as they are unable to respond appropriately to DNA damage.

Question 52

Why is the p53 gene often referred to as the “guardian of the genome”?

Answer 52

The p53 gene is often called the “guardian of the genome” because of its crucial role in maintaining genomic integrity. It regulates cell-cycle checkpoints and apoptosis in response to DNA damage, preventing the proliferation of damaged cells.

Question 53

What is the significance of the RB1 (retinoblastoma 1) tumor-suppressor gene in cancer development?

Answer 53

The loss or mutation of the RB1 tumor-suppressor gene contributes to the development of various cancers, including those of the breast, bone, lung, and bladder.

Question 54

How was the RB1 gene initially identified, and what disorder is associated with its studies?

Answer 54

The RB1 gene was originally identified through studies on retinoblastoma, an inherited disorder leading to the development of tumors in the eyes of young children. Retinoblastoma occurs at a frequency of about 1 in 15,000 individuals.

Question 55

What role does the retinoblastoma protein (pRB) play in the cell cycle?

Answer 55

The retinoblastoma protein (pRB) controls the G1/S cell-cycle checkpoint, regulating the transition from G1 to S phase.

Question 56

How does the activity of the pRB protein vary throughout the cell cycle?

Answer 56

The pRB protein is nonphosphorylated in the G0 phase, inhibiting transcription factors like E2F. During G1 phase, it becomes phosphorylated by the CDK4/cyclin D1 complex, releasing bound regulatory proteins and allowing the expression of genes needed for the G1 to S phase transition.

Question 57

What is the state of the pRB protein in the G0 phase, and how does it affect transcription factors?

Answer 57

In the G0 phase, the pRB protein is nonphosphorylated and binds to transcription factors like E2F, inactivating them.

Question 58

Describe the phosphorylation of the pRB protein during the cell cycle.

Answer 58

Throughout the G1 phase, the pRB protein becomes phosphorylated by the CDK4/cyclin D1 complex, leading to the release of bound regulatory proteins.

Question 59

What happens to the pRB protein after cells traverse S, G2, and M phases?

Answer 59

After cells traverse S, G2, and M phases, the pRB protein reverts to a nonphosphorylated state. It binds to regulatory proteins such as E2F, keeping them sequestered until needed for the next cell cycle.

Question 60

What are the three major checkpoints in the cell cycle affected by genetic defects in cancer cells?

Answer 60

Genetic defects in cancer cells affect the G1/S, G2/M, and M checkpoints in the cell cycle.

Question 61

What happens at the G1/S checkpoint, and how does it regulate cell cycle progression?

Answer 61

At the G1/S checkpoint, the cell monitors its size and checks for DNA damage. If the cell is not of adequate size or if DNA is damaged, progression through the cell cycle is halted until these conditions are corrected.

Question 62

Describe the conditions monitored at the G2/M checkpoint and the consequences of failure.

Answer 62

At the G2/M checkpoint, physiological conditions in the cell are monitored before mitosis. If DNA replication or repair is incomplete, the cell cycle arrests until these processes are finished.

Question 63

What is the role of the M checkpoint in mitosis, and what conditions are monitored?

Answer 63

The M checkpoint, during mitosis, monitors the successful formation of the spindle fiber system and the attachment of spindle fibers to kinetochores associated with centromeres. If spindle fibers are improperly formed or attachment is inadequate, mitosis is arrested.

Question 64

important regulating protein in the cell cycle

Answer 64

Cyclins and cyclin-dependent kinases (CDKs)-

Question 65

When a cyclin is present, it binds to a

Answer 65

specific CDK, triggering activity of the CDK/cyclin
complex.

Question 66

How does the cell cycle progress in response to cyclin and CDK activity?

Answer 66

yclins accumulate and are destroyed in a precise pattern during the cell cycle. When a cyclin is present, it binds to a specific CDK, forming a complex that phosphorylates and activates proteins necessary for advancing the cell through the cell cycle.

Question 67

an example of CDK/cyclin complexes and their functions during the cell cycle.

In G1 phase, it complexes activate proteins that stimulate transcription of genes required for DNA replication during S phase.

Answer 67

CDK4/cyclin D

Question 68

In G1 phase, phosphorylates proteins involved in early mitosis events, such as nuclear membrane breakdown and chromosome condensation.

Answer 68

CDK1/cyclin B,

Question 69

: How is mitosis completed, and what role does cyclin B play in this process?

Answer 69

Mitosis can only be completed when cyclin B is degraded, reversing the protein phosphorylations characteristic of M phase. Cyclin B is essential for events like nuclear membrane breakdown, chromosome condensation, and cytoskeletal reorganization during early mitosis.

Question 70

How can mutation or misexpression of genes controlling the cell cycle contribute to cancer development?

Answer 70

Mutation or misexpression of genes controlling the cell cycle, such as those involved in the G1/S or G2/M checkpoints, can lead to continuous cell growth and division without repairing DNA damage. This accumulation of mutations may result in the loss of control over proliferation, contributing to cancer development.

Question 71

How does the accumulation of mutations in genes controlling cell proliferation or metastasis occur?

Answer 71

As cells with mutated G1/S or G2/M checkpoint genes continue to divide, they accumulate mutations in genes whose products control cell proliferation or metastasis.

Question 72

What happens if genes controlling progress through the cell cycle, such as those encoding cyclins, are expressed at the wrong time or incorrect levels?

Answer 72

the cell may grow and divide continuously and may be unable to exit the cell cycle into G0.

Question 73

What is the outcome when a cell loses control over proliferation due to mutations in cell cycle control genes?

Answer 73

The result is that the cell loses control over proliferation and is on its way to becoming cancerous.

Question 74

is a genetically controlled process wherein the cell commits suicide.

Answer 74

Apoptosis

Question 75

If DNA replication, repair, or chromosome assembly is defective, what do normal cells do?

Answer 75

halt their
progress through the cell cycle until the condition is corrected. This reduces the number of
mutations and chromosomal abnormalities that accumulate in normal proliferating cells.

Question 76

What is the second line of defense initiated by cells in response to severe DNA or chromosomal damage?

Answer 76

In response to severe DNA or chromosomal damage where repair is impossible, cells may initiate apoptosis, also known as programmed cell death.

Question 77

Apart from preventing cancer, in what other context is apoptosis initiated during normal multicellular development?

Answer 77

Apoptosis is initiated during normal multicellular development to eliminate certain cells that do not contribute to the final adult organism. An example is during the development of fingers and toes.

Question 78

How is the rate of mutations influenced, and what plays a crucial role in mutation correction?

Answer 78

The rate of mutations is influenced not only by their occurrence but also by the efficiency of correction through DNA-repair systems.

Question 79

What is the association between defects in DNA repair genes and cancer?

Answer 79

Defects in genes encoding components of DNA repair systems have consistently been associated with various cancers.

Question 80

Provide an example of a condition related to a defect in nucleotide-excision repair and its impact on DNA damage correction.

Answer 80

People with xeroderma pigmentosum, who are defective in nucleotide-excision repair, lack the ability to efficiently correct DNA damage caused by mutagens, including ultraviolet light.

Question 81

In colorectal, endometrial, and stomach cancers, what repair system is often found to be defective?

Answer 81

n about 13% of colorectal, endometrial, and stomach cancers, cells are defective in mismatch repair, a significant repair system in the cell.

Question 82

How can the inappropriate activation of telomerase contribute to cancer progression?

Answer 82

The inappropriate activation of telomerase can contribute to cancer progression.

Question 83

What happens to the telomeres in most somatic cells with each cell division?

Answer 83

Answer: In most somatic cells, the ends of chromosomes cannot be replicated, and the telomeres become shorter with each cell division.

Question 84

Why are somatic cells capable of only a limited number of cell divisions?

Answer 84

The shortening of telomeres with each cell division eventually leads to the destruction of chromosomes and cell death, limiting somatic cells to only a limited number of divisions.

Question 85

In many tumor cells, what mutation allows for the indefinite division of cells?

Answer 85

In many tumor cells, mutations in sequences that regulate the expression of the telomerase gene occur, allowing the enzyme to be expressed and the cell to divide indefinitely.

Question 86

: What is the current understanding of the precise role of telomerase in tumor progression?

Answer 86

: Although the expression of telomerase appears to contribute to the development of many cancers, its precise role in tumor progression is unknown and is under investigation.

Question 87

Why is angiogenesis crucial for the progression of tumors?

Answer 87

Angiogenesis, the growth of new blood vessels, is crucial for supplying oxygen and nutrients essential for the survival and growth of tumors.

Question 88

How is angiogenesis stimulated in normal cells, and what is its regulation based on?

Answer 88

Angiogenesis in normal cells is stimulated by growth factors and proteins encoded by genes with carefully regulated expression.

Question 89

What distinguishes the expression of genes involved in angiogenesis in tumor cells compared to normal cells?

Answer 89

In tumor cells, genes encoding proteins for angiogenesis are often overexpressed compared to normal cells.

Question 90

What may happen to inhibitors of angiogenesis-promoting factors in tumor cells?

Answer 90

In tumor cells, inhibitors of angiogenesis-promoting factors may be inactivated or underexpressed.

Question 91

Provide an example of an inherited cancer related to angiogenesis, and what gene mutation is involved?

Answer 91

Von Hippel–Lindau disease

Question 92

an inherited cancer where individuals develop multiple types of tumors, is caused by the mutation of a gene that affects angiogenesis.

Answer 92

Von Hippel–Lindau disease