Brainscape's Knowledge GenomeTM

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


See full index

MOD Midterm > Neoplasia: Molecular Basis of Cancer > Flashcards

Neoplasia: Molecular Basis of Cancer Flashcards

1
Q

To go from a normal cell to cancer cell, we need to create a clone; what is the first thing we are going to do in order to do this?

A

we create a mutation that is divergent enough from the normal cell to be promoting cancer, but not too divergent that it kills the cell

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

after the initiating mutation, what happens next to make cancer?

A

you add on additional driver mutations

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

What are the four general types of gene classes that are responsible for oncogenesis?

A

proto-oncogenes, tumor-suppressor genes, apoptosis-regulating genes, DNA repair genes

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

What are germline mutations?

A

heritable; early mutations present as the gametes are providing the genetic material for an embryo to form; all cells in offspring carry 1 mutated allele

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

What are somatic mutations?

A

non-heritable; involve an original combination of chromosomes that have no mutation whatsoever; mutation only in cells of affected area

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

How do we make cancer from proto-oncogenes?

A

they gain function and become oncogenes

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

how do we make cancer from tumor-suppressor genes?

A

they lose function (so there is no tumor suppression)

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

how do we make cancer from apoptosis-regulating genes?

A

suppress apoptosis/cell death

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

how do we make cancer from DNA repair genes?

A

they lose function (so if there is DNA damage, they can no longer repair it)

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

What is the difference between driver vs. passenger mutations?

A

driver mutations are causal; passenger mutations contribute to cancer growth, but does not establish cancer

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

What is the genetic evolution of cancer?

A

the first mutation allows it to become a malignant clone, but even more mutations can evolve and there can be quite a heterogenous cell population

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

what are oncogenes?

A

mutated genes that result in excessive cell growth

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

what are oncoproteins?

A

the result of the genetic mutation

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

What is the mode of activation in the proto-oncogene PDGFB? and what occurs when this happens?

A

overexpression; astrocytoma

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

What is the mode of activation for the proto-oncogene ERBB1 (EGFR)? and what occurs when this happens?

A

mutation; adenocarcinoma of the lung

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

what is the mode of activation for the proto-oncogene ERBB2 (HER)? and what occurs when this happens?

A

Amplification; breast carcinoma

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

what is the mode of activation for the proto-oncogene KRAS? and what occurs when this happens?

A

point mutation; colon, lung, and pancreatic tumors

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

What is the mode of activation for the proto-oncogene MYC? and what occurs when this happens?

A

Translocation; Burkitt lymphoma

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

what is the mode of activation for the proto-oncogene NMYC? and what occurs when this happens?

A

Amplification; Neuroblastoma

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

What could be the functional product of an activated proto-oncogene (mutated)?

A

abnormal protein, excessive amount of protein, novel protein,

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

What happens when there is an amplification of growth factor/ growth factor receptor? and what is a common example of this?

A

Her-2/neu (aka ERBB2); this amplification results in too many proteins being expressed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Too much Her2 generates what?

A

too many protein receptors, which signals for cancer cells to divide and multiply

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

How can we treat amplification of growth factor/growth factor receptor (e.g. Her-2)?

A

we can treat with a receptor antibody called Herceptin

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

What happens when there are point mutations of KRAS?

A

the system is chronically and dramatically on for the downstream signaling (theres too much downstream signaling)

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

In a normal state, what is the favored state of RAS?

A

it tends to be in the inactivated GDP bound state; will be activated in a pulsatile manner- will be activated when it is supposed to be and then turn off again when it is not being used

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

what happens in the mutated RAS associated with cancer?

A

it defaults to the GTP-bound state- there is activation of the downstream signaling; RAS mutations can cause it to be “stuck” in the GTP-bound state

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

Mutations of RAS that contribute to oncogenesis bind it in a _____________?

A

constitutively active state (constantly active)

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

What is a characteristic feature of the mutations that occur in RAS?

A

they contribute to oncogenesis by binding it in a constitutively active state

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

what is PTEN?

A

a negative regulator of cell signaling- so if cancer wants to have uncontrolled cell growth, it needs to down regulate PTEN

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

What mutation is given to PTEN to allow cancer?

A

a loss of function mutation - so it can no longer provide its normal inhibitory function

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

What cancer is strongly associated with initiating mutations causing loss of function of PTEN?

A

endometrial carcinoma

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

What is BCR-ABL and how is it formed?

A

a hybrid gene; ABL comes from chromosome 9 and joins BCR from chromosome 22

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

what happens when BCR-ABL is formed?

A

there is now a tyrosine kinase that is now going to be extremely active inside the cell (its a non-receptor tyrosine kinase)

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

what happens when the non-receptor tyrosine kinase is upregulated?

A

it is directly feeding into the signaling pathways creating cellular proliferation

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

What is BCR-ABL known as and what is it associated it?

A

the philadelphia chromosome; commonly associated with CML

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

What does oncogene addiction mean?

A

when tumor genesis is extremely dependent on a particular oncoprotein (e.g. BCR-ABL)

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

Why is knowing particular oncogene addictions important?

A

for treatment- if you are dependent on this mechanism, it is a target for therapy for cancer

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

What is a very effective form of treatment for CML? and why?

A

tyrosin kinase inhibitors (imatinib); because of oncogene addiction

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

Is oncogene addiction very common with different cancers?

A

no; CML is a very specific circumstance where we are able to cut out the supplier with this one little snip

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is MYC?

A

the master transcriptional regulator; this gets out of hand with several tumors; you don’t want too much MYC because it leads to cancer

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

What is the most common extracranial solid tumor in children?

A

neuroblastoma

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

There are two ways the cyclins can become carcinogenic. What are these?

A

we can turn on the “on” switch or we could turn off the “off” switch

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

What normally inhibits the cyclin pathway?

A

p16

44
Q

what can germline loss of function of p16 lead to?

A

familial melanomas

45
Q

what cyclin is overexpressed in certain cancers such as mantle cell lymphoma?

A

cyclin D1

46
Q

what are three examples of tumor suppressor genes in normal cells?

A

RB, TP53, and APC

47
Q

what happens when RB, TP53, or APC become mutated?

A

they can no longer function as normal, so they cannot suppress tumors

48
Q

How do RB and TP53 shut down proliferation?

A

by causing senescence and apoptosis

49
Q

What is Knudson’s hypothesis?

A

two mutations involving both alleles of RB are required to produce retinoblastoma; in germline (familial) mutations, only one additional somatic hit is needed; in sporadic cases, a particular cell has to have 2 somatic mutations to knock out both genes

50
Q

germline mutations of RB mean all cells have a pre-existing mutation; these cells are at high risk of what?

A

tumorigenesis by succumbing to a second hit

51
Q

What is RB a key negative regulator of?

A

the G1/S cell cycle transition

52
Q

What does RB exist as in quiescent cells?

A

in an active hypophosphorylated state

53
Q

what does RB exist as in cells passing through the G1/S cell cycle transition?

A

inactive hyperphosphorylated state

54
Q

when RB is hyperphosphorylated, what helps usher in the growth cycle?

A

the cyclins

55
Q

what do high levels of cyclins lead to?

A

hyperphosphorylation of RB and therefore inhibition of RB

56
Q

what happens if you have a loss of function of RB?

A

inappropriate activation of the cell cycle

57
Q

What is TP53 known as?

A

the guardian of the genome

58
Q

What is the most frequently mutated gene in human cancers?

A

TP53

59
Q

what cancers are classically positive for p53 mutations?

A

serous adenomas of the ovary

60
Q

what happens if there is a loss of function mutation in p53?

A

there will be no cell cycle arrest; no DNA repair; no senescence–> leads to malignant tumors

61
Q

We treat cancers with radiation and chemotherapy; these should work by inducing DNA damage, but what happens if the p53 is not working/mutated?

A

these tumors have a higher requirement for therapy

62
Q

What syndrome is associated with the germline TP53 mutation?

A

the Li-fraumeni syndrome

63
Q

what differentiates a germline mutation from a somatic mutation of p53?

A

younger age, diverse tumors, and a family history

64
Q

Besides TP53 and RB, what is another tumor suppressor gene we discussed?

A

APC: adenomatous polyposis coli

65
Q

germline mutations of APC are associated with what?

A

familial adenomatous polyposis- polyps develop early and extensively; colectomy in early adulthood or cancer is consider inevitable by 40 years of age

66
Q

What is special about germline mutations of APC?

A

they can occur de novo; so you cannot rely on a family history

67
Q

APC is a component of what signaling pathway?

A

WNT signaling pathway

68
Q

what is a major function of the APC protein?

A

to hold beta-catenin function in check

69
Q

what happens during WNT signaling?

A

it blocks the formation of the destruction complex- so beta-catenin can translocate from the cytoplasm to the nucleus and cause cell proliferation

70
Q

What happens if there is no APC/ mutated APC?

A

the destruction complex will not form- Beta-catenin will be able to signal cell proliferation

71
Q

What is the Warburg effect?

A

aerobic glycolysis

72
Q

What does autophagy in cancer allow?

A

doesn’t really help with growth, but it does help with survival

73
Q

How do cancer calls evade cell death?

A

they mutate/down regulate TP53 and they upregulate BCL-2

74
Q

What cell death pathway is important for killing cancer cells?

A

the intrinsic apoptotic pathway

75
Q

What is the opposite of fertility?

A

senescence

76
Q

What determines senescence?

A

telomeres

77
Q

What do stem cells have that prevent senescence?

A

telomerase- an enzyme that protects their telomeres

78
Q

What is the relationship with cancer and telomeres?

A

cancer also uses telomerase so that it will never be unable to replicate

79
Q

What are cancer stem cells?

A

like normal stem cells- they can self renew- give rise to heterogenous populations of daughter cells and proliferate extensively

80
Q

Solid tumors cannot grow more than a few mm unless they induce what?

A

angiogenesis

81
Q

Tumors set up their vascular system how?

A

by switching the tumor microenvironment from antiangiogenic to proangiogenic (an angiogenic switch)

82
Q

What is a proangiogenic factor?

A

HIF1

83
Q

what is the effect of HIF1?

A

VEGF and FGF

84
Q

how could you treat cancer when thinking about angiogenesis?

A

block VEGF- this would block the process of angiogenesis from occurring

85
Q

What are the three major steps in invasion and metastasis?

A

Getting through the basement membrane, getting into the vessels, getting out of the vessels

86
Q

How does the tumor initiate getting through the basement membrane?

A

there will be dissociation of tumor cells from each other

87
Q

how do the tumors cells dissociate from each other?

A

an epithelial to mesenchymal transition

88
Q

what are the hallmarks of epithelium?

A

in epithelial tumors, there are cadherins that are responsible for binding these cells to each other

89
Q

what occurs during the epithelial to mesenchymal transition?

A

the silencing of the E-cadherins

90
Q

After the epithelial to mesenchymal transition, what occurs next?

A

the degradation of the ECM basement membrane and connective tissue

91
Q

how do cancer cells accomplish the degradation of the ECM basement membrane and connective tissue?

A

with enzymes called Matrix Metalloproteinases

92
Q

what occurs after the degradation of the ECM basement membrane and connective tissue?

A

attachment and locomotion and invasion into the vessel

93
Q

What is the major cell responsible for the immune defense against tumors (tumor antigens)?

A

CD8+ Cytotoxic T lymphocytes

94
Q

Although we have CD8+ CTLs to help defend against tumor cells, some tumor cells have a way around this. What do they do?

A

antigen loss (failure to produce tumor antigen) and class I MHC-deficient tumor cells–> both lead to lack of recognition by t cell; tumor cells can also produce immunosuppressive proteins or expression of inhibitory cell surface proteins –> leads to inhibition of t cell activation

95
Q

What is an example of an immunosuppressive protein or expression of inhibitory cell surface proteins that tumor cells present to t cells to inhibit their activation?

A

PD-1 Ligand

96
Q

How can we treat tumor cells with the over expression of inhibitory cell surface proteins?

A

by using PD-1/PD-1 Ligand antibodies–> immune checkpoint inhibitors

97
Q

what does failure of the mismatch repair lead to?

A

unstable, persistent microsatellites in the DNA (microsatellite instability)

98
Q

What is Lynch syndrome?

A

germline loss of function mutations in a mismatch repair gene (remember that failure of the mismatch reapir leads to microsatellite instability)

99
Q

what do lynch syndromes include?

A

colorectal, stomach, pancreas, ovary and uterus, prostate gland, and the urinary tract

100
Q

How might DNA damage (like strand breaks) be repaired?

A

by the homologous recombination repair (HRR)

101
Q

what are the responsible genes for HRR?

A

BRCA-1 and BRCA2

102
Q

what is a treatment for acute promyelocytic leukemia?

A

all trans retinoic acid (since the PML/RAR complex doesn’t “like” retinoic acid anymore

103
Q

What are the 2 major mechanisms of epigentics?

A

DNA methylation and Histone modification

104
Q

what is the role of miRNA (micro RNA)?

A

to regulate RNA

105
Q

what happens if we down regulate miRNAs?

A

the translation of RNA will go up (and this includes oncogenic RNA)

106
Q

when is an example of when cancer utilizes down regulation of miRNAs?

A

with BCL-2s–> miRNAs are in part responsible for keeping BCL-2 in check; so when you have downregulation of the miRNAs for BCL2, you will have upregulation of the actual BCL2 molecule

MOD Midterm (22 decks)

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