Genetics of Cancer Oncogenes and Tumor Suppressors Flashcards
(133 cards)
1
Q
A ____ mutation enable proto-oncogenes to become oncogenes.
A
gain-of-function
2
Q
When ___ or ___ don’t work properly, they can allow cells to grow out of control and cause cancer.
A
proto-oncogenes; tumor suppressor genes
3
Q
The transcription of RNA to DNA is done through the enzyme ____.
A
reverse transcriptase
4
Q
What is one of the main pathways that gives rise to colon cancer?
A
Wnt/B-catenin signaling pathway
5
Q
Tobacco use can lead to what types of cancers?
A
mouth
lung
kidney
bladder
6
Q
What happens if there is a gene amplification mutation in a proto-oncogene?
A
a normal protein may be greatly overproduced
7
Q
When cells are stressed, what do they not want to do?
A
divide
8
Q
What type of cancers arise from epithelial cells?
A
carcinomas
9
Q
____ are normal genes that slow down cell division, repair DNA mistakes, and tell cells when to die.
A
Tumor suppressor genes
10
Q
The ___ protein is produced when cells are stressed.
A
p16
11
Q
When do tumors become malignant?
A
once they escape their site of origin
12
Q
What happens if there is a regulatory mutation of a proto-oncogene?
A
a normal protein may be greatly overproduced
13
Q
What was the first viral oncogene discovered and identified?
A
Rous Sarcoma Virus (RSV)
14
Q
What happens if there are reduced levels of Rb in the cell?
A
there won’t be enough Rb protein to control the actions of E2F, but p16 will be at normal levels in a stressed cell, inhibiting cyclin-CDK as it should, but because the Rb brake isn’t there, the cell will divide in a stressed environment
15
Q
The chromosomal translocation associated with Chronic Myelogenous Leukemia (CML) is known as the ____.
A
Philadelphia chromosome
16
Q
The oncogenic mutation from valine to ____ on the Her2 receptor causes dimerization and formation of a ligand-independent receptor oncoprotein.
A
glutamine
17
Q
The control mechanisms of cancer cells are ____, in that they are unable to halt or control cell division.
A
defective
18
Q
DNA tumor viruses tend to target the ____.
A
tumor suppressor genes
19
Q
What happens to B-catenin when the Wnt ligand is not bound to the receptor?
A
B-catenin is sequestered and phosphorylated inside the cell and DEGRADED by the proteasome
20
Q
How is the paradoxical contraindication of Rb explained?
A
only one single tumor cell is required to produce a tumor, so any individual who has inherited a mutant Rb allele takes only one more “hit” to create a tumor
21
Q
Are Apc, p53, TGFB receptor II, Smad4, and MLH1 oncogenes or tumor suppressors?
A
tumor suppressors
22
Q
Are cancer cells less prone to undergo apoptosis?
A
YES
23
Q
What happens to B-catenin when the Wnt ligand is bound to the receptor?
A
GSK-3B is phosphorylated and inactivated, allowing B-catenin to build up in the cytoplasm and translocate to the nucleus
24
Q
____ are benign cancers that arise from cartilage.
A
Chondromas
25
What happens if there is a deletion or point mutation in the coding sequence of a proto-oncogene?
a hyperactive protein may be made in normal amounts
26
What type of benign tumor is from epithelial cells and have a glandular organization?
adenomas
27
The ____ creates a fusion gene of the BCR and ABL genes.
Philadelphia chromosome
28
Ligand-independent cell division gives rise to ___.
tumors
29
The myeloid stem cell lineage gives rise to what types of blood cells?
red blood cells
platelets
myeloblasts
granulocytes (N, E, B)
30
How is breast cancer classified?
- Primary Tumor (TX - T4)
- Lymph Node Status (NX - N3)
- Metastases (MX - M1)
31
____ tumors develop invasiveness.
Malignant
32
When cells are stressed they don't want to divide. Which protein is produced?
p16
33
The Rb mutation displays a ___ penetrance.
reduced
34
What keeps cells from dividing and expressing S-phase genes when stressed?
p16 inactivates the cyclin-CDK kinase which in turn prevents active Rb surrounding E2F from being phosphorylated and deactivated, thereby preventing E2F from being released and activated to allow DNA synthesis
35
Is a high-grade intraepithelial neoplasia considered benign or malignant?
benign - hasn't progressed into connective tissue yet
36
Influenza is a ____ virus. Why does this cause us to create a new flu vaccine each year?
RNA; due to reverse transcriptase, the flu mutates very quickly
37
One mutant Rb allele is considered ____ at the level of the individual, but ____ at the level of the cell.
dominant; recessive
38
Breast cancer is an ____ syndrome.
autosomal dominant
39
Cancer stem cells generally divide more ____ and may survive radiation and chemotherapy.
slowly
40
What cells normally control what kind of cell it is and how often it grows and divides?
proto-oncogenes
41
____ is tightly packed DNA; ____ is DNA that has been unwound.
Heterochromatin; euchromatin
42
Estrogen receptors, Her2 receptors, and EGF receptors are all involved in ___.
breast cancer
43
What is cancer maintained by?
a population of cancer stem cells
44
Active ___ protein provides a safety brake on cell proliferation.
p53
45
What type of growth factor do cancer cells secrete a lot of? Why is this significant?
VEGF; VEGF is very important in angiogenesis
46
What cells do we extract DNA from if we are using blood?
white blood cells
47
The ligand-____ dimerization of the receptor, therefore activating the intracellular signaling WITHOUT the ligand present.
independent
48
How might a normal Rb gene be eliminated?
- nondisjunction causes chromosome loss
- chromosome loss, then duplication
- mitotic recombination
- gene conversion
- deletion
- point mutation
49
ABL is a ___ that becomes activated and leads to CML.
proto-oncogene
50
Why can't we extract DNA from red blood cells?
red blood cells don't have a nucleus
51
___ changes are changes in the DNA sequence, such as a nucleotide change.
Genetic
52
What type of tumor remains contained in the tissue from which they originated?
benign tumors/growths
53
Viral protein ___ can expose E2F and allow cell proliferation.
E7
54
Can you still develop a tumor if normal cell death is taking place?
YES - if there is increased cell division with normal apoptosis
55
Why are there often cancer relapses or long, complicated therapies?
because radiation and chemotherapy target rapidly dividing cells and not the slowly-dividing cancer stem cells
56
___ protein binds to E2F to brake the cell cycle.
Rb
57
What type of cancer arises from the glial cells of the CNS?
gliomas
58
Blood stem cells give rise to the ___ and ___ stem cell lineages.
myeloid; lymphoid
59
A diet high in fat, low in fiber, and containing fried and broiled foods is associated with what kinds of cancer?
bowel
pancreas
prostate
breast
60
It is the strong ____ to develop a tumor that is inherited as a dominant trait.
predisposition
61
Is cancer inherited?
NO - but cancer-predisposing mutations can be
62
Most inherited mutations associated with cancer affect a person's ___.
risk for developing cancer
63
____ induce help from normal stromal cells in their microenvironment.
Cancer cells
64
What happens if there is a chromosomal rearrangement in a proto-oncogene?
a normal protein may be overproduced or fusion to a transcribed gene produces a hyperactive fusion protein
65
___ are derived from lymphatic tissue.
Lymphomas
66
____ are derived from white blood cells and their precursors (hematopoietic cells).
Leukemias
67
When p16 is bound to CDK, can the cyclin bind?
NO
68
___, when stable and active, is involved in cell cycle arrest, senescence, and apoptosis.
p53
69
Is a single mutation enough to cause cancer?
NO
70
What happens to a cell when p16 is not present or has been mutated and inactivated?
the cyclin-CDK complex will form and phosphorylate the Rb protein, which will allow E2F to express S-phase genes
71
What happens if there is a mutation in any of the B-catenin degradation complex components?
there is unopposed, un-ligand activated B-catenin signaling, which can lead to cancer
72
Tobacco use and alcohol use are associated with ___ and ___ cancer.
mouth; throat
73
What happens when there are mutations to the p16 gene?
cell cycle arrest does not occur normally; the function of p16 and its regulatory regions do not function normally and can lead to cancer
74
Are K-ras and B-catenin oncogenes or tumor suppressors?
oncogenes
75
What are some other considerations when assessing breast cancer?
if it is noninvasive or invasive and hormone receptor status
76
How can a proto-oncogene become activated?
- deletion or point mutation
- regulatory mutation
- gene amplification
- chromosome rearrangment
77
Skin tags and moles are examples of ____.
benign growths
78
What type of cancer cells do radiation and chemotherapy typically target?
rapidly dividing cells
79
Normally, _____ receptor proteins are monomers, single path transmembrane-spanning proteins that have a binding receptor on the extracellular side that bind one ligand.
proto-oncogene
80
If p53 is knocked out, what would happen to the cell?
none of the signals that would normally induce cell death would be detected, so the damaged cells would continue to proliferate
81
In this type of cancer, bone marrow produces excessive amounts of abnormal granulocytes at the expense of other healthy white blood cells.
Chronic Myelogenous Leukemia (CML)
82
___ have a high penetrance and contain a high risk of cancer.
Rare variants
83
DNA being inappropriately packaged into heterochromatin rather than euchromatin is an example of a ____ change.
epigenetic
84
RNA tumor viruses tend to target the ____.
oncogenes
85
With Wnt signal, what happens to the Wnt-responsive genes?
they are transcribed or "turned on"
86
Cancer or tumor formation is often a ____ event involving other mutations and environmental factors.
somatic
87
The Hepatitis viruses can promote the development of ___ cancer.
liver
88
A ___ mutation functionally eliminate the tumor suppressor genes to stimulate cell survival and proliferation.
loss-of-function
89
Can cancer cells survive and proliferate in foreign sites?
YES
90
___ induces cell cycle arrest or apoptosis.
p53
91
What gene is the intracellular component of the degradation complex of the B-catenin signaling pathway?
APC
92
At what level is control lost in the cell when the Her2 or EGF receptors dimerize and allow activation without the ligand actually present?
at the receptor level
93
If p16 is bound to CDK and cyclin cannot bind, what protein is not able to be activated?
inactive E2F
94
The ___ receptor can lose its extracellular domain, dimerize and its intracellular domains can activate signaling.
EGF
95
___ infects CD+ T-cells, macrophages, and microglial cells.
HIV
96
The ___ protein is a universal cell cycle regulator.
Rb
97
What are some things that can cause gene inactivation?
- accidental nucleotide change
- euchromatin into heterochromatin
- methylation of nucleotides
98
A diet low in vegetables, high in salt, and high in nitrate can lead to what kinds of cancers?
stomach
| esophagus
99
___ is a CDK inhibitor.
p16
100
What signals can be detected by p53 that would lead to cell cycle arrest or apoptosis?
- hyperproliferative signals
- DNA damage
- telomere shortening
- hypoxia
101
What are the 3 ways cancer genes are classified?
1) genes that normally inhibit cellular proliferation
2) genes that activate proliferation
3) genes that participate in DNA repair
102
Do cancer cells stabilize their telomeres? How so?
YES - they produce telomerase or acquire other means to stabilize their telomeres
103
How do cancer cells induce help in their microenvironment?
by secreting hormones and factors via autocrine and paracrine fashion to induce the desired effects
104
Oncogenes occur as a result of ____; tumor suppressor genes that cause cancer occur as a result of ____.
activation; inactivation
105
Viral protein ___ can inactivate p53 and remove the "brake" on cell proliferation.
E6
106
Most oncogenes have normal cellular homologs called ___ that function as cell growth regulators.
proto-oncogenes
107
What cells are in the white blood cell population?
```
Neutrophils
Eosinophils
Basophils
B lymphocytes
T lymphocytes
Natural killer cells
```
108
Are cancer cell genetically stable?
NO - they are unstable
109
Can children inherit changes that occur in somatic cells?
NO
110
Do cancer cells induce angiogenesis?
YES
111
Most tumors seem to go through the ___ pathway.
p53
112
Tumors secrete angiogenic signals which promote the formation of new ____.
blood vessels
113
What type of cancers arise from connective tissue or muscle cells?
sarcomas
114
Without Wnt signal, the Wnt-responsive genes are ___.
off
115
____ are more self-sufficient than normal cells.
Cancer cells
116
New blood vessels prompted by cancerous cells do 2 things. What are they?
- supply the tumor with more nutrients
| - provide a means of metastasis which can colonize distant sites
117
Rb protein binds the cell proliferation factor ___.
E2F
118
How many polymorphisms do we have in our genome? Are they dangerous?
thousands; NO
119
What molecule gives rise to colon cancers?
APC
120
Cancer cells are relatively ____ to anti-proliferative extracellular signals.
insensitive
121
HIV's RNA genome is bound to key enzymes, such as ____.
reverse transcriptase
protease
ribonuclease
integrase
122
____ are the mutated form of certain normal genes of the cell called proto-oncogenes.
Oncogenes
123
What happens when a proto-oncogene mutates?
it turns into an oncogene that activates when it shouldn't and can allow proliferative growth and cancer
124
How are malignant tumors classified?
according to the tissue or cell type from which they originated
125
Can viruses have a DNA or RNA genome?
EITHER
126
___ growth and progression generally involves multiple, successive rounds of genetic changes, ending with clonal selection of a cell that produces cancer.
Tumor
127
What cells does the lymphoid stem cell lineage give rise to?
B lymphocytes
T lymphocytes
Natural killer cells
128
What causes a malignant tumor from a viral DNA fragment?
when it accidentally gets incorporated into the host genome (and not just within the cell)
129
What type of cell can lead to the cancerous stem cell population?
normal stem cells that become afflicted
130
___ changes are alterations outside the genetic sequence, such as issues with regulation.
Epigenetic
131
What does activated E2F allow for?
progression into the S phase
132
What are the two mechanisms in which tumors arise?
- increased cell division with normal apoptosis
| - normal cell division with decreased apoptosis
133
____ have a low penetrance and have a low risk of developing cancer.
Common variants
