Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Genetics > The non-inherited genome and cancer > Flashcards

The non-inherited genome and cancer Flashcards

1
Q

What is cancer and what causes it?

A

Cancer is the uncontrolled growth of abnormal cells in the body, caused by mutations that alter the function or regulation of genes involved in cell proliferation, cell death, (unregulation of mitosis and apoptosis), dna repair and other vital proccesses.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How can our genomes (that are relatively stable) acquire mutations over time?

A

Errors of replication or mutagenic agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

The vast majority of mutations that occur are what type?

A

Silent point mutations - little or no functional effect on genes they occur in - They are neutral because they do not change the amino acids in the proteins they encode.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can a series of ongoing mutations lead to that will eventually result in cancer

A

An activating mutation of one of the two alleles of a proto-oncogene converts it to an oncogene, which can induce transformation in cultured cells or cancer in animals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is cellular transformation

A

the genetic alteration of a cell (normal cell transforms to cancer cell)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a passenger mutation?

A

a mutation that has no effect on the fitness of a clone but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are cell numbers?

A

Product of the rates of cell division (mitosis) and cell death (apoptosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are cell numbers regulated?

A

Controlling the rate of cell division and death of all cells within an organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why do cells die/produce constantly?

A

EXHAUSTION MOSTLY - cells don’t last very long as they undergo a tough job if we look at the functional gut cells - replaced so rapidly - gut exposed to a lot of stresses (toxins, food, ph changes) don’t last long! You are replaced - which is why you have a lot of mitosis in certain areas and then alot of apoptosis to balance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are new cells produced and how do old cells die?

A

New cells - precise duplication of contents of existing cell followed by cell division to form two daughter cells (mitosis)
Old cells - triggering a regulated cell death process known as apoptosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How can cancer be caused by this unregulation of cell numbers?

A

normal controls on processes that regultae cell numbers within tissues are lost.
Gene mutations - affect rate of mitosis and apoptosis and leads to accumulation of extra cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does cancer incidence vary between tissues?

A

Cancer’s are most common in epithelial cells than non epitehelial cells such as sacromas, blood-forming and CNS and PNS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Is cancer a single disease?

A

No, it is a diverse group of conditions that all share a common increase in cell numbers within particular tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cancer can be split into two groups, what are they?

A

Benign (fail to spread to other tissues - non life threatening)
Malignant (cancer is invasive and spreads to other tissues within the body)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Cancers can arise from practically any tissue, but which tissue is the most common and why?

A

Epithelial -

1) highest risk of exposure to carcinogens because the cells line the surfaces of body that are in direct contact with environment (skin, lungs, mouth, stomach, intestine) and the environment is a major source of carcinogens.
2) epithelial cells are highly mitotic - have high replacement rate because they are prone to damage (exposure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is epithelial tissue?

A

sheets of cells that form the upper layer of skin and line the walls of cavities and tubes within the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are carcinomas?

A

cancers that arise from epithelia (these tumours are resp for 80% of all cancer-related deaths in western world)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are tumours?

A

groups of abnormal cells that form lumps or growths (neoplasia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

When does a tumour become cancerous?

A

A tumour is cancerous when it: grows into nearby tissues (malignant), has cells that can break away and travel through the blood or lymphatic system and spread to lymph nodes and distant parts of the body.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Does cancer refer to a benign or malignant tumour?

A

Malignant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are carcinogens and give examples?

A 
A carcinogen is any agent that directly increases the incidence of cancer. Cancer causing agents - any substance, radionuclide, or radiation that promotes carcinogenesis, the formation of cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes.
chemical carcinogens (including those from biological sources), physical carcinogens, and oncogenic (cancer-causing) viruses.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Give an example of oncogenic viruses (carcinogen)

A

Examples include human papillomaviruses, the Epstein-Barr virus, and the hepatitis B virus, all of which have genomes made up of DNA. Human T-cell leukemia virus type I (HTLV-I), which is a retrovirus (a type of RNA virus), is linked to tumour formation in humans.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Give an example of physical carcinogens

A

Physical carcinogens include ultraviolet rays from sunlight and ionizing radiation from X-rays and from radioactive materials in industry and in the general environment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Give examples of chemical carcinogens

A

inhaled asbestos, certain dioxins, and tobacco smoke.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Cancers arise more frequently in what type of tissues and why?

A

Highly mitotic - cells are already dividing at rel high rate and barriers to cell division are lower than in non dividing tissues (post-mitotic tissues)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Do all cells in the body divide at the same rate?

A

No, some exhibit low rates of cell division - brain and muscle tissue..heart (very stable - don’t hear much talk of cancer here.. may migrate there from other tissues)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Give examples of common cancers of epithelial origin

A

Adenocarcinoma - lung, colon, breast, esophagus

Squamous cell carcinoma - skin, lung, esophagus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is adenocarcinoma and squamous cell carcinoma?

A

a malignant tumour formed from glandular structures in epithelial tissue, histolgoical type
originates from squamous cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What does histological type mean?

A

type of tissue in which the cancer originates (histological type)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are sarcomas?

A

Malignant tumours (cancers) that arise from non-epithelial tissues, arise from the various connective tissues (account for 1% tumours encountered in cancer clinics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Give an example of sarcomas

A

Bone and soft tissue sarcomas are the main types of sarcoma. Soft tissue sarcomas can develop in soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. They can be found in any part of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the three types of tissues that cancer can arise from?

A

Carcinomas - Epithelial
Sarcomas - Non-Epithelial
Blood forming (hematopoietic) tissues
Neuroectodermal tumours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What are heamtopoetic tissue cancers?

A

Blood-forming tissues and cells of the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Give examples of hematopoietic malignancies

A

leukaemias and lymphomas (17% cancer related deaths)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What type of cancer causes the most deaths?

A

Carcinomas, then heamatopoetic, neuroectdermal tumours, then sarcomas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are neuroectodermal tumours?

A

Tumours arise from various components of the central (.ie brain) and peripheral nervous systems (ie, spinal chord) and outlying nerve tissue (account for 17% cancer related deaths)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is a mutation?

A

Alteration to the most commonly found coding sequence (wild type sequence) of a protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Are all mutations bad?

A

Obviously not, we evolve because of mutations. Mutations can increase the activity of a protein or decrease it or generate the opposite function (some have no effect - silent).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How is a protein like a bike?

A
  • proteins are comprised of different domains (sim to diff parts of bicycle) - some of which critical to function and others less
  • if we have malfunctions (mutations) in some parts of bike, some would be critical while others would not (break bell or light - wouldn’t affect function, remove wheel or chain it would. puncture tyre - slow down bike but not cause it to stop functioning completely. removing brakes would not be immediate problem, lead to serious consequences in certain circumstances)
  • THUS consequences of gene mutations can be serious, mild, or of little consequence depending on what part of protein is affected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Consequences of gene mutations can be serious, mild, or of little consequence depending on what?

A

what part of protein is affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

The types of mutations that can have diff consequences (serious, mild, no consequence) are what?

A

Loss-of-function mutations
Gain-of-function mutations
Dominant-interfering mutations (dominant-negative)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are loss-of-function mutations?

A

Reduction in the function of the protein encoded by the gene which can be complete (complete loss of function, null mutation or knockout) or incomplete/partial (hypomorphic mutation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are tumor surpressor genes?

A

Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death).

44
Q

What happens when loss of function mutation occurs in tumor surpressor genes?

A

Loss of function - protein is downregulated due to loss of function mutation so cell division can get out of control.

45
Q

What are gain-of-function mutations?

A

Activity of the resulting protein is increased

  • protein can become more stable
  • bind to its substrate better
  • resist an inhibitor better
  • expressed at higher level so more abundant!!
46
Q

What occurs when a gain of function mutation occurs in a proto-oncogene?

A

When a mutation occurs in a proto-oncogene, it becomes permanently turned on (activated). The gene will then start to make too much of the proteins that code for cell growth. These mutations are also considered dominant mutations

47
Q

What are proto-oncogenes?

A

A normal gene involved in the process of cell growth which, when altered by mutation, becomes an oncogene that can contribute to cancer.

48
Q

Give examples of oncogenes

A

ras

myc

49
Q

Give examples of tumour surpressor genes

A

p53

p21

50
Q

What are dominant-interfering mutations?

A

Dominant mutations lead to a mutant phenotype in the presence of a normal copy of the gene and acts antagonistically to the wild-type allele

51
Q

How does the protein oppose the function of the wild type protein?

A
  • binding to it or its target (which could be another protein or DNA) AND
  • blocking its function
52
Q

Where are dominant-interfering mutations commonly seen?

A

where a molecule functions as a dimer, trimer or other oligomer

53
Q

How does p53 loses function due to dominant-interfering mutations?

A

P53 protein - tetramer.
if single subunit of tetramer is mutated, whole tetramer loses function - mutant pf53 that binded to tetramer acts as dominant-interfering mutant (look at diagram on page 4)

54
Q

How does Ras gain of function mutation increase its activity?

A

Ras - crystal structure, gain of function mutation occurs which increases the likelyhood that Ras will be in its active (GTP-bound state)

55
Q

What is cancer incidence?

A

Number of people who get cancer

56
Q

Are all carcinogens mutagenic agents?

A

Most, but not all carcinogens are mutagens.

57
Q

What is a mutagen/mutagenic agent?

A

mutagen is a physical or chemical agent that changes the genetic material and thus increases the frequency of mutations (cause genetic mutation)

58
Q

Do the vast majority of mutations lead to cancer?

A

No, due to :

  • DNA damage detection and repair mechanisms
  • mechamisims that limit ability of abornmal cells to replicate (including simple eliminiation of these cells by apoptosis, as well as induction of non-replication state caled senescence)
59
Q

How do viruses provoke cancer?

A

Through insertion into genome of their hosts

1) viral genome may carry gene that enables host cell to escape normal controls placed to restrict cell division and/or life span
2) virus may integrate its genome close to a host gene that regulates cell division and/or apoptosis - result in aberrant expression of such genes

60
Q

How can we conclude that cancer is an uncommon ocurrence?

A
  • 10 trillion cells in body
  • total number of cells produced in lifetime is 1000 times this number (due to replacement) - huge potential for mutations to occur in any one of these cells (accidental mutation or external mutagens)
61
Q

What are monoclonal tumours?

A

Arisen from a single precursor cell that has become cancerous

62
Q

Evidence for monoclonal tumours

A
  • Studying tumours derived from B cells (immune system produce antibodies) were monoclonal in nature, suggested tumours arose from a single cancerous progenitor
  • analysis of chromosmal lesions found in many cancers
63
Q

Why is only a single type of antibody made by each individual B cell?

A

Antibody genes are shuffled to generate unique combinations and this occurs randomlu during the maturation of each B cell (VDJ recombination)

64
Q

How does studying tumours derived from B cells provide evidence that most tumours are monoclonal

A

potential of immune ysstem to produce diff antibodies is limitless, but only a single type of antibody is made by each indiv B cell. B cell tumours - produce many diff antibodies (specific for antigens) if arose from multiple independently transformed B cells (single cells)

65
Q

How does the analysis of chromosmal lesions found in many cancers provide evidence that most tumours are monoclonal?

A

Reveal that all cells of the tumour with typically display the same lesion.
Philadelphia (Ph) chromosome found in chronic myeloid leukemia and results in translocation of BCR gene (and ass promoter) upstream of the AbI gene to create a new fusion gene (Bcr-AbI), the protein product of which displays greately increased kinase activity

66
Q

What is a polyclonal tumour?

A

two or more cells or clones of cells interact to initiate a tumor

67
Q

What are germline mutations (inherited cancer)?

A

germline mutation occurs in a sperm cell or egg cell. It passes directly from a parent to a child at the time of conception. As the embryo grows into a baby, the mutation from the initial sperm or egg cell is copied into every cell within the body. Because the mutation affects reproductive cells, it can pass from generation to generation.

68
Q

How is cancer a multi-step proccess

A

not one, but several, mutations are required to cause cancer due to mechanisms that have evolved to prevent Each mutation drives a wave of cellular multiplication associated with gradual increases in tumor size, disorganization and malignancy. - stepwise accumulation of independent mutations over a long period of time

69
Q

Why does cancer occur more often in older people.

A

Usually, cancer occurs from multiple mutations over a lifetime. They have had more opportunities for mutations to build up.

70
Q

How many mutations are expected to cause a tumour?

A

6-8 independent mutations

71
Q

What is the exception to the rule that “Cancer is a multi-step process”

A

Large-scale chromosomal breakage - produce multiple mutations simultaneously as a result of faulty chromosomal repair - chromothripsis (2.5% of all cancers).

72
Q

What is chromothripsis?

A

Large-scale chromosomal breakage that produces multiple mutations simultaneously as a result of faulty chromosomal repair

73
Q

What are oncogenes?

A

Gene that, in mutated form, promotes cancer

74
Q

Mutations in what type of genes contributes to the development of cancer

A

Oncogenes and tumor surpressor genes

75
Q

What are oncogenic mutations?

A

Mutations of host genes that enhance proliferation and/or other biological properties that increase the likelihood of cancer

76
Q

What are the barriers to transformation? (prevent individual cells from proliferating in an uncontrolled manner)

A

1) Requirement for growth factors
2) Tumour suppressor genes act as brake on proliferation
3) Requirement for oxygen and nutrients
4) Immune system

77
Q

Why do cells require growth factors?

A

To enable them to divide

78
Q

What provides cells with growth factors?

A

Normally by other cells (in a paracrine manner)

79
Q

How do cancer cells inc supply of growth factors?

A

1) acquiring the ability to make growth factors themselves
2) mutating the downstream signalling molecules asociated with the binding of growth factors to their membrane receptors such that the receptors appear to be constantly switched on

80
Q

So many cell divisions, why doesn’t cancer happen more often?

A

Due to barriers of transformation -

1) Requirement for growth factors
2) Tumour suppressor genes act as brake on proliferation
3) Requirement for oxygen and nutrients
4) Immune system

81
Q

What is a growth factor?

A

naturally occurring substance capable of stimulating cellular growth

82
Q

What is one of the most important tumour surpressor genes

A

p53 transcription factor - collaborates with proteins like ATM, ATR, Chk1, Chk2 involved in DNA damage detection and repair

83
Q

How does p53 transcription factor suppress uncontrolled proliferation and act as a barrier to transformation?

A

1) When p53 is activated within cells (through stabilisation of the normally-labile p53 protein) it induces transcription of genes that block entry into mitosis - enables DNA repair to be carried out before cell is permitted to re-initiate mitosis
2) Extensive DNA damage results in p53-dependent expression genes (Noxa, Puma and Bax) that promote aptosis and eliminate the cell completely.

84
Q

Why does loss of p53 function greatly accelerate the progression of cancer?

A

Crucial role it plays in monitoring the integrity of the genome.. (blocks entry of mitosis, apoptosis)

85
Q

The p53 gene is found in mutant form in what percentage of cancers?

A

50% of all cancers

86
Q

Why do tumours require new blood vessels?

A

To acquire a supply of oxygen and nutrient in order to grow beyond a certain size (1cm^3)

87
Q

What is a major restraint upon the growth of solid tumours and how do they overcome it?

A

the ability to induce the growth of new blood vessels is a major step in cancer progression and is often linked to production of VEGD (vascular endothelial growth factor) by the tumour. (neo-vascularization) - induce new blood vessels to grow (angiogenesis) or cells of the tumour will die due to hypoxia and nutrient deprivation

88
Q

What is hypoxia?

A

lack of oxygen

89
Q

How does the immune system act as a barrier against transformation?

A

Vertebrates and other high organisms possess immune systems capable of recognising aberrant cells that may be expressing mutated proteins or cells that fail to express proteins that are normally expressed by healthy cells.
Cytotoxic T cells and natural killer cells have evolved to patrol the body to weed out cells (by killing cells via apoptosis) that are displaying mutant or ‘foreign’ proteins. such cells serve an important defense against the development of cancer

90
Q

How does cancer arise in terms of the number of mutations..

A

Series of step-wise changes where cells become progressively more transformed due to accumulation of different mutations

91
Q

Describe how the development of cancer happens over a long time frame..

A

Pre-cancerous cell undergoes a process of progressive transformation from a state from a relatively non-cancerous state to a progressively more transformed cancerous state. At each point along the way, further mutations occur (facilitated by previous mutations) that enable cells to progress to the next stage.

92
Q

How can the long time frame of the development of cancer be accelerated?

A

If pre-existing mutations can be inherited that already provide a fertile soil upon which further mutations can develop.

93
Q

What is transformation in relation to cancer?

A

Used to describe the various stages of the progression to cancer
Progression of a cell from a normal to a cancerous state

94
Q

Transformed cells display various properties that are not typically displayed by normal cells, what are these characteristics and why is this useful?

A

1) Ability to grow in lab cultures (in vitro) for long periods of time
2) Reduced requirement for growth facyors
3) Anchorage-independence
4) Altered morphology
5) Loss of contact inhibition
6) Ability to form tumors when introduced into immunocompromised mice
Useful for discovery of genes that are involved in cancer development

95
Q

Why are growth factors essential for cell division?

A

These ptoreins bind ot cell surface receptors and switch on signalling cascades that promote division of cells

96
Q

What is a convenient source of growth factors?

A

Serum - when added to cells is able to promote division of most cell types.

97
Q

Serum (source of growth factors) is sometimes added to cultures of cells to promote cell division, however untransformed cells will undergo set number of cell divisions (25-30) and become unresponsive, why?

A

Due to an inbuilt clock that limits the number of divisions such cells can undergo before entering a state known as Replicative senescence. If you go any more, it will enter this state.

98
Q

What is replicative senescence

A

irreversible arrest (stops) of cell proliferation (inc no. cells) and altered cell function. It is controlled by multiple dominant-acting genes.

99
Q

What does replicative senescence depend on?

A

depends on the number of cell divisions, not time. depends on the cell type and on the species and age of the donor

100
Q

What is the limit called of a cell before it enters replicative senescence?

A

Hayflick limit

101
Q

Why do we have a hayflick limit?

A

Relates to the shortening of chromosome ends (telomeres) during each successive round of cell division. At some point the telomeres become so eroded that further chromosomal duplication becomes impossible and cells can no longer undergo division. Such cells often display chromosomal fusions, breakages and other abberations

102
Q

In terms of cancer cells being able to grow for a long time, how does this differ from normal cells

A

They can surpass the hayflick limit - a hallmark of transofrmation is the ability to continue to divide well beyond this limit.

103
Q

How can transformed cells surpass the hayflick limit?

A

Related to the expression of an enzyme (telomerase) that can repair telomeres and therefore greatly enhance the number of cell divisions that a cell expressing this enzyme can undertake.

104
Q

Telomerase expression is normally confined to what kind of cells?

A

embyronic cells or stem cells buy many cancers display reactivation of telomerase gene expression which increases the number of cell divisions such cells can undergo

105
Q

What factor is critical for initiation of cell division?

A

Growth factors

106
Q

In relation to growth factors, what is the difference between transformed and untransformed cells?

A

Reduced requirement of growth factors

  • grow their own factors (autocrine growth)
  • greatly amplify the number of growth factor receptors expressed by the cell as this has the effect of mimicking growth factor receptor engagement
  • acquire mutations in genes that function in growth factor receptor signalling pathways, such that the signalling cascade is permanently switched on (Ras and B-raf mutations found in many cancers)

Genetics (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions