Chapter 8: Genetics of Cancer Flashcards Preview

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1
Q

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.

A

cancer

2
Q

Two fundamental properties of can cells:

A

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

3
Q

types of tumor:

A

benign and malignant tumor

4
Q

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.

A

Benign tumor

5
Q

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

A

Malignant tumor

6
Q

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?

A

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.

7
Q

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

A

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).

8
Q

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.

A

Familial Adenomatous Polyposis (FAP)

9
Q

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

A

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

10
Q

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

A

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.

11
Q
A
12
Q

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

A

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

13
Q

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

A

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

14
Q

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

A

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

15
Q

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

A

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.

16
Q

What is the percentage of human cancers associated with viruses?

A

15 percent of human cancers are associated with viruses.

17
Q

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

A

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

18
Q

Is virus infection alone sufficient to trigger human cancers?

A

No

19
Q

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

A

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

20
Q

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

A

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.

21
Q

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

A

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

22
Q

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

A

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

23
Q

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

A

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

24
Q

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

A

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

25
Q

Name a synthetic chemical carcinogen found in cigarette smoke.

A

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

26
Q

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

A

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

27
Q

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

A

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

28
Q

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

A

nitrosamines

29
Q

can cause DNA lesions that lead to cancer.

A

Radiation (X rays, ultraviolet light)

30
Q
  • produced from normal metabolism creates oxidative end products that can
    damage DNA, proteins, and lipids.
A

free radicals

31
Q
  • stimulates tissue repair and cell division, resulting in
    DNA lesions accumulating during replication.
A

Chronic inflammation due to infection-

32
Q

What do proto-oncogenes encode?

A

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

33
Q

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

A

oncogene

34
Q

What is the function of tumor-suppressor genes?

A

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

35
Q

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

A

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.

36
Q

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

A

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

37
Q

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

A

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.
38
Q

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

A

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

39
Q

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

A

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.

40
Q

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

A

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.

41
Q
  • The most frequently mutated gene in human cancers— mutated in more than 50 percent
    of all cancers
A

p53 Tumor-Suppressor Gene

42
Q

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

A

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.

43
Q

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

A

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.

44
Q

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

A

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.

45
Q

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

A

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.

46
Q

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

A

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.

47
Q

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

A

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.

48
Q

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

A

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.

49
Q

What happens in cancer cells lacking sufficient p53 regarding apoptosis?

A

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.

50
Q

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

A

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.

51
Q

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

A

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

52
Q

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

A

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.

53
Q

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

A

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.

54
Q

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

A

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.

55
Q

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

A

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

56
Q

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

A

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.

57
Q

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

A

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

58
Q

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

A

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

59
Q

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

A

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.

60
Q

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

A

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

61
Q

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

A

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.

62
Q

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

A

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.

63
Q

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

A

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.

64
Q

important regulating protein in the cell cycle

A

Cyclins and cyclin-dependent kinases (CDKs)-

65
Q

When a cyclin is present, it binds to a

A

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

66
Q

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

A

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.

67
Q

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.

A

CDK4/cyclin D

68
Q

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

A

CDK1/cyclin B,

69
Q

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

A

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.

70
Q

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

A

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.

71
Q

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

A

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.

72
Q

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

A

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

73
Q

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

A

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

74
Q

is a genetically controlled process wherein the cell commits suicide.

A

Apoptosis

75
Q

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

A

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.

76
Q

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

A

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

77
Q

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

A

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.

78
Q

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

A

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

79
Q

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

A

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

80
Q

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

A

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.

81
Q

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

A

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

82
Q

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

A

The inappropriate activation of telomerase can contribute to cancer progression.

83
Q

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

A

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

84
Q

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

A

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.

85
Q

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

A

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.

86
Q

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

A

: 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.

87
Q

Why is angiogenesis crucial for the progression of tumors?

A

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

88
Q

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

A

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

89
Q

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

A

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

90
Q

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

A

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

91
Q

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

A

Von Hippel–Lindau disease

92
Q

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

A

Von Hippel–Lindau disease