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Applied Biochemistry > Genetics of Cancer: Oncogenes and Tumor Suppressors > Flashcards

Genetics of Cancer: Oncogenes and Tumor Suppressors Flashcards

(108 cards)

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1
Q

types of genetic diseases (4)

A

chromosome disorders
single gene disorders
multifactorial or complex
sex linked and mitochondrial

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2
Q

chromosome disorders (4)

A

rearrangements/translocations
deletions
insertions
duplications

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3
Q

single gene disorders (3)

A

dominant
recessive
codominant

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4
Q

multifactorial or complex (2)

A

multiple genes

gene environment

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5
Q

Chronic Myelogenous Leukemia (CML)

A

Bone marrow produces excessive amounts of abnormal granulocytes at the expense of the other healthy white blood cells

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6
Q

The Philadelphia chromosome, creates a fusion of the (2) genes

A

BCR and ABL

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7
Q

BCR

A

break point cluster region

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8
Q

BCR + ABL =

A

oncogene

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9
Q

what lineages can the blood stem cell differentiate into?

A

myeloid

lymphoid

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10
Q

is a single mutation enough to cause cancer?

A

no

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11
Q

while cancer predisposing mutations can be (and often are) —, cancer or tumor formation is a — — involving other mutations and environmental factors

A

inherited

somatic event

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12
Q

most inherited mutations associated with cancer affect a persons

A

risk for developing cancer

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13
Q

can caner be inherited?

A

no, it is somatic. it can increase your risk of developing cancer, but that doesn’t mean you will get it because it takes multiple things to accumulate

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14
Q

tumor growth and progression generally involves

A

multiple, successive rounds of genetic changes with the end results of natural selection of a clonal cel that produces a tumor or cancer

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15
Q

rumors can arise from (2)

A

increased cel division

decreased apoptosis

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16
Q

normal cell division and normal apoptosis leads to

A

homeostasis

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17
Q

increase cell division and normal apoptosis leads to

A

tumor

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18
Q

normal cell division and decreased apoptosis leads to

A

tumor

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19
Q

tumors can arise from (2) changes

A

genetic

epigenetic

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20
Q

penetrance

A

how many people that inherit a genetic change experience the phenotype

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21
Q

we carry different variants of genes, with different

A

penetrance

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22
Q

higher relative risk associated with rare, high-penetrance genetic variants, such as mutations in the — genes associated with hereditary breast and ovarian cancer and the mismatch repair genes associated with Lynch syndrome

A

BRCA1/ BRCA2

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23
Q

how are malignant tumors classified

A

according to the tissue or cell type from which they originated

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24
Q

carcinomas

A

cancers arising from epithelial cells

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25
sarcomas
arise from connective tissue or muscle cells
26
leukemias
derive from WBC and their precursors (hematopoietic cells)
27
gliomas
derive from glial cells of the CNS
28
benign tumors are
likewise classified
29
adenomas
benign epithelial tumors with glandular organization
30
chondromas
arise from cartilage
31
benign tumor
tumor contained within tissue they originated in
32
malignant tumor
tumor moves out of tissue it originated in to invade/metastasize
33
risk factors for cancer (5)
occupational exposure tobacco related diet (low in vegetables, high salt, high nitrate) diet (high fat, low fiber, fried and broiled foods tobacco and alcohol
34
top 2 % of total cases
``` tobacco related (24) diet (high fat, low fiber, fried and broiled foods) (37) ```
35
many cancers are maintained by a population of
cancer stem cells
36
cancer stem cells generally divide
more slowly
37
cancer stem cells may survive
radiate and or chemotherapy as these treatments generally target more rapidly dividing cells
38
tumors secrete --- signals
angiogenic
39
tumor angiogenic signals promote the formation of new
blood vessels need to supply the nutrient needs of the growing tumor
40
these new blood vessels also provide a means by which --- can colonize distant sites
metastasis
41
cancer cells are more --- --- than normal cells
self sufficient
42
cancer cells are relatively insensitive to
anti-proliferative extracellular signals
43
cancer cells are less prone to undergo
apoptosis
44
cancer cells are defective in the control mechanisms that normally
halt cell division
45
cancer cells induce help from normal --- cells in their microenvironment
stromal
46
cancer cells induce
angiogenesis
47
cancer cells can survive and proliferate in
foreign sites
48
cancer cells are genetically
unstable
49
cancer cells produce --- or acquire another means of ...
telomerase | stabilizing their telomeres
50
classification of cancer genes (3)
genes that normally inhibit cellular proliferation genes that activate proliferation genes that participate in DNA repair
51
Oncogenes
mutated forms of certain normal genes of the cell called proto-oncogenes
52
Proto-oncogenes are often genes that normally control
what kind of cell it is and how often it grows and divides
53
When a proto-oncogene mutates (changes) into an oncogene, it
turns on or activates when it is not supposed to be
54
When this occurs, the cell can grow out of control, leading to ---
cancer
55
Tumor suppressor genes are normal genes that (3)
slow down cell division repair DNA mistakes tell cells when to die (apoptosis or programmed cell death)
56
When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to ---
cancer
57
An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the --- of proto-oncogenes, but tumor suppressor genes cause cancer when they are ---
activation (turning on) | inactivated (turned off)
58
RB1
Rb protein binds to E2F to brake cell cycle
59
p16
CDK inhibitor
60
p53
inhibits cell cycle arrest or apoptosis
61
APC
intracellular component of degradation complex of beta-catenin signaling pathway
62
BRCA1 interacts with --- repair protein
RAD51
63
BRCA2 interacts with --- repair protein
RAD51
64
what did Alfred Knutson invent
2 hit hypothesis of Rb
65
Knudson’s original hypothesis was that
a person needed to acquire two mutant copies of the Rb gene
66
This could be accomplished by a (2)
germline mutations inherited from one parent (carrier) and then a somatic second mutation/event in the normal allele
67
The Rb protein is a “universal” cell cycle ---
regulator
68
Normal Rb protein functions as a
brake on cell cycle progression
69
One mutant Rb allele is considered --- at the level of the individual, but --- at the level of the cell
dominant | recessive
70
other considerations (4)
type hormone receptor status ki-67 proliferation index her2/neu status
71
The somewhat paradoxical contradiction can be explained by realizing that
only a single tumor cell is required to produce a tumor, and in any individual who has inherited a mutant Rb allele it takes only a second hit in one cell to create a tumor
72
Thus it is the strong predisposition to develop a tumor that is inherited as a --- trait
dominant
73
The Rb mutation also displays reduced ---, only about --% of individuals who inherit the mutant allele experience a second hit and develop a tumor
penetrance | 90
74
The p16 protein (product of the INK4 gene) is produced when cells are --- and is an important component of the cell cycle --- that should normally occur
stressed | arrest
75
Mutations that inactivate the function of p16 or mutations in regulatory regions of the p16 gene that --- --- can also contribute to cancer
shutdown expression
76
one of the most common mutations in cancer
p53
77
what can lead to activation of p53 (4)
hyper proliferative signals DNA damage telomere shortening hypoxia
78
types of breast cancer (2)
invasive | noninvasive
79
noninvasive (2)
* ductal carcinoma in situ (25% of all B.C) | * lobular carcinoma in situ
80
invasive (3)
Usually epithelial • Ductal (65-85% of Invasive) • Lobular (5-10% of invasive) • Other (10% of invasive)
81
hormone receptor status (2)
* ER + or – | * PR + or –
82
-
wont respond
83
+
drugs to treat tumors are more effective
84
increased risk genes of breast cancer (3)
BRCA1 (breast cancer 1, early onset) BRCA2 (breast cancer 2, early onset) TP53 (p53)
85
BRCA1/2 pedigree
autosomal dominant syndrome
86
APC mutations give rise to
colon cancer release of beta Catelin from degradation complex, goes to the nucleus, cell growth stimulation
87
high % of colon cancers have mutations in (2)
APC | p53
88
Unlike the genomes of all eukaryotic and prokaryotic cells, virus genomes can be found either in the form of (2)
DNA or RNA
89
Virus genomes can be (2)
single-stranded or double-stranded | linear or circular
90
~15% of human cancers world-wide are thought to arise from mechanisms that involve (3)
viruses, bacteria or parasites
91
two types of viruses
``` RNA viruses (RNA genome, retrovirus) DNA viruses (DNA genome) ```
92
first viral oncogene identified
from the avian rout sarcoma virus (RSV)
93
oncogene=
cancer genes
94
most oncogenes have normal cellular homologs called
porto-oncogenes
95
protconcogenes function as
regulators of cell growth
96
protooncogenes include (4)
growth factors growth factor receptors signal transduction molecules transcription factors
97
DNA virus examples (4)
HPV hep B hep C herpesvirus family (Epstein Barr virus)
98
RNA virus examples (2)
human T cell leukemia virus type 1 | human immunodeficiency virus
99
HIV infects (3)
CD+ T-cells, macrophages and microglial cells
100
Virus particle consists of 2 identical copies of the
HIV positive single- | stranded RNA genome
101
The RNA genome is bound to several proteins including key enzymes such as --- ---, which is needed to create a DNA copy of the HIV genome. Others include (3)
reverse transcriptase | proteases, ribonucleases and integrase
102
The HIV genome consists of -- structural landmarks (regions) and generally -- genes that encode -- proteins
7 9 (sometimes 10) 19
103
Upon entry into the cell, the reverse transcriptase copies the RNA genome into a --- and eventually into a --- that enters the nucleus and integrates into the host cell genome
ss-cDNA | ds-cDNA
104
Because reverse transcriptase has a high error rate this results in a
high frequency of mutations in the cDNA copies
105
influenza virus
8 segments of negative single-stranded RNA that exist in a complex with various nucleoproteins.
106
The 8 RNA strands code for -- proteins
11
107
The negative sense RNA is transcribed into a positive sense RNA (cRNA), which serves as a template for (2)
protein synthesis and for negative strands that are incorporated into new viral particles
108
Influenza virus does not use a DNA copy and as RNA is much less stable than DNA and as such --- at a faster rate than any other kind of virus
mutates

Applied Biochemistry (52 decks)

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