Neoplasia Flashcards
1
Q
A
2
Q
severe dysplasia involving the full thickness of the epithelium without penetrating the basement membrane is referred to as what?
A
carcinoma in situ
3
Q
does hematogenous spread of neoplasia more often involve intravasation of veins or arteries?
A
veins - thinner walled
4
Q
which two organs are the most common sites for hematogenous spread of a tumor?
A
liver and lung
5
Q
what is the difference in mutations of proto-oncogenes (gain of function mutations), and mutations in tumor suppressor genes (loss of function mutations), genetically speaking?
A
generally, one mutated allele is enough to drive tumorigenesis in mutations of protooncogenes whereas 2 mutated alleles are typically required for mutations in tumor suppressor genes to contribute to tumorigenesis (the exception being haploinsufficiency)
6
Q
BRAF is the protoncogene for which protein involved in signal transduction?
A
RAS
7
Q
RAS, PI3K, MYC, and D-cyclin are all examples of which type of oncoproteins?
A
growth factor receptors
8
Q
what inhibits RAS activation?
A
GAPs
9
Q
what inhibits PI3K?
A
PTEN and phosphatase
10
Q
what is the receptor for TGF-a?
A
EGFR
11
Q
what is the most important receptor type for growth factors?
A
Receptor tyrosine kinases
12
Q
what are the two downstream signaling cascades activated by RAS?
A
The MAPK cascade and the PI3K/AKT pathway
13
Q
a gain of function mutation in BRAF has down stream effects in which signaling pathway?
A
MAPK
14
Q
AKT and MTor are part of which downstream pathway of RAS activation?
A
PI3K
15
Q
where are non receptor tyrosine kinases located?
A
cytoplasm or the nucleus
16
Q
the chimeric BCR-ABL protein has constituitive activity of which receptor type?
A
tyrosine kinase (ABL)
17
Q
a tumor that is highly dependent on a single oncogene is called what?
A
oncogene addicted
18
Q
upregulation of which TF proto-oncogene is associated with the Warburg effect?
A
MYC
19
Q
which TF protooncogene upregulates expression of telomerase?
A
MYC
20
Q
What is the outcome of a gain of function mutation in CD4K or cyclin D in a cell?
A
unrestricted progression through the G1 restriction point in the cell cycle
21
Q
what is the role of CDK4 and Cyclin D? What inhibits this role?
A
phosphorylates RB protein allowing cell to progress through G1 restriction point. Inhibitors include the INK4 inhibitor - p16
22
Q
which CDK inhibitor is induced by the tumor suppressor p53?
A
p21
23
Q
which CDK inhibitor responds to growth suppressors such as TGF-b?
A
p27
24
Q
which CDK inhibitor increases p53 levels by inhibiting MDM2 (a ubiquitin ligase that degrades p53)?
A
P14
25
what effect does phosphorylation of Rb have on progression through the cell cycle?
phosphorylation inactivates Rb allowing the cell to progress through the G1-S transition
26
Tumor suppressor gene APC inhibits which signaling pathway?
WNT
27
Tumor suppressor gene NF1 inhibits which signaling pathway?
RAS/MAPK
28
Tumor suppresor gene PTCH inhibits which signaling pathway?
Hedgehog
29
Tumor suppresor gene PTEN inhibits which signaling pathway?
PI3K/AKT signaling
30
SMAD2 and SMAD4 are involved in which signaling pathway? which oncogenes do they suppress?
involved in TGF-b signaling, suppress MYC and CDK4
31
Tumor suppressor gene CDKN2A encodes which proteins?
p16 (inhibits CDK4/6) and p14 (indirectly inhibits Rb)
32
The tumor suppressor gene VHL inhibits which TF?
HIF1a
33
TP53 is a tumor suppressor gene that encodes which protein?
p53
34
What type of DNA damage do tumor suppressors BRCA1 and BRCA2 repair?
DS breaks
35
what type of DNA damage do tumor suppressor MSH2, MLH1, MSH6 repair?
DNA mismatch repair
36
What role do E2F TF have on cell cycle progression?
E2F transcription factors are normally bound to hypophosphorylated Rb. When Rb is phosphorylated by CDK4/6-Cyclin D and CDK2-Cyclin E, E2F is released and drives expression of genes needed to progress to S1
37
which 2 growth factors promote the activation of Cyclin D-CDK4/6 and Cyclin E-CDK2?
EGF, PDGF
38
The E7 protein of HPV has what effect on the cell cycle?
E7 protein binds and inhibits Rb allowing unchecked progression through G1-S
39
What are the two key initiators of p53 following DNA damage and hypoxia?
ATM and ATR
40
Which protein is bound to p53 in its hypophosphorylated state?
MDM2
41
which is the key initiator of p53 following oncogenic cellular stress?
p14/ARF which binds MDM2 and displaces p53 to allow its levels to rise
42
transient p53 induced cell cycle arrest in response to DNA damage induces the production of which DNA repair protein?
GADD45
43
during p53 induced apoptosis, p53 promotes the production of which pro-apoptosis genes?
BAX and PUMA
44
When WNT is bound to FRZ, what happens with b-catenin and APC?
B-catenin is stabilized and translocates to the nucleus to initiate transcription of cyclin D1 and MYC
45
when WNT is not bound to FRZ, what happens with b-catenin?
In the absence of WNT signaling, b-catenin is bound to APC to form the "destruction complex" which leads to B-catenin degradation
46
B-catenin is involved in the WNT/FRZ pathway and which other pathway?
E-cadherin
47
A mutation of B-catenin/Ecadherin pathway is associated with which feature of carcinomas?
loss of contact inhibition
48
CDH1 is the tumor suppressor gene encoding which protein?
E cadherin
49
mutational inactivation of SMAD4 is common in which type of cancer?
pancreatic
50
in the presence of oxygen, HIF1a is bound to which tumor suppressor gene to cause its ubiquitination and degradation?
VHL
51
Why do tumor cells "prefer" to utilize anaerobic respiration vs. oxidative phosphorylation for metabolism (i.e. the Warburg effect)
Glycolysis provides the tumor cells with metabolic intermediates (carbon moieties) which the tumor cell uses to synthesize cellular components, aerobic glycolysis does not
52
"oncometabolism" is driven by which enzyme?
IDH
53
mutant IDH inhibit TET family proteins which lead to which type of DNA changs?
epigenetic changes (DNA methylation, histone modification)
54
loss of p53 prevents the upregulation of which pro-apoptotic protein thereby inhibiting apoptosis?
PUMA
55
cellular senescence is associated with the upregulation of which 2 tumor suppressor genes?
p53, INK4a/p16
56
which method of DNA repair joins chromosomes where there are double stranded breaks if p53 is inactivated?
nonhomologous end-joining
57
nonhomologous end-joining leads to which cycle culminating in mitotic catastrophe (in the absence of telomerase) or, cancer (in the presence of telomerase)?
bridge-fusion cycle
58
how does the tumor suppressor p53 suppress angiogenesis?
by stimulating the expression of anti-angiogenic molecules like thrombospondin 1 and repressing the stimulation of VEGF
59
SNAIL and TWIST are TFs associated with which process?
EMT
60
Which MMP cleaves type IV collagen?
MMP9
61
Expression of which adhesion molecule may enhance spread of circulating neoplastic cells to lymph nodes?
CD44
62
PTHrp stimulates osteoblasts to produce which ligand?
RANKL
63
Which cell is most important for anti-tumor immunity?
CTL
64
what is the purpose of cross-presentation of tumor antigens by dendritic cells?
to allow the tumor to be killed by CTLs
65
As a means of evading the immune response, tumor cells may promote the expression of which inhibitory receptor on T-cells?
CTLA-4
66
as a means of evading the immune response, tumor cells may increase the expression of which surface protein that inhibits T-cell activation
PD-1 ligand
67
which DNA repair mechanism repairs DNA with mismatched base pairs?
DNA mismatch repair proteins
68
microsattelite instability is a hallmark of which type of DNA defect?
mismatch-repair defect
69
DNA damaged by UV radiation is repaired via which mechanism?
nucleotide excision repair
70
covalent DNA cross links and double stranded DNA breaks are repaired through which mechanism?
homologous recomination
71
what is the most common mechanism of proto-oncogene activation?
chromosomal translocation
72
In Burkitt lymphoma, MYC is translocated close to which gene?
the IGH gene - leads to constituitive expression
73
In order for gene translocation to occur, two double stranded DNA breaks need to happen. During which process is this expected to happen in lymphocytes?
during normal receptor gene recombination or class switching recombination
74
retinoiic acid therapy used in patients with acute promyelocytic leukemia is an example of what type of therapy?
differentiation therapy
75
The BCR-ABL fusion gene has constiuitive activity of which receptor?
tyrosine kinase
76
small extrachromosomal structures called double minutes OR homogenous staining regions can be seen microscopically and are characteristic of which type of genomic alteration?
amplification
77
what is the role of miRNAs?
inhibition of mRNA
78
DNA adduct formation is part of which step of cancer development (initiation or promotion?)
initiation
79
direct acting carcinogens are typically ________. Weak or strong carcinogens?
Weak
80
alkylating agents are an example of which type of carcinogen?
direct acting
81
are "ultimate" carcinogens indirect or direct acting?
indirect acting
82
Which form of UV light is believed to be responsible for the induction of cutaneous cancers?
UVB
83
which tissues are most susceptible to radiation induced neoplasia?
thyroid (in young animals/children), hematopoetic cells then breast, lungs, salivary gland
84
The E6 protein in viral papillomas degrades p53 and stimulates which enzyme?
TERT - which is a telomerase
85
the E7 protein in viral papillomas binds to Rb and displaces which proteins?
E2F proteins (it also inactivates p21 and p27)
86
Deficiency of which vitamin is associated with metaplasia?
Vitamin A
87
are preneoplastic changes (hyperplasia, hypertrophy, metaplasia, dysplasia) generally irreversible or reversible?
generally reversible
88
is anaplasia a reversible or irreversible change?
generally irreversible
89
a pre-invasive form of carcinoma that remains within the epithelial structure from which it arises and does NOT penetrate the basement membrane is what?
carcinoma in situ
90
carcinomas that stimulate significant desmoplasia are called what?
scirrhous
91
Melanocytes, adrenal medullary cells, schwann cells, ganglion cells all arise from which tissue type?
Neural crest
92
what is a "mixed tumor"
A tumor containing multiple cell types
93
disorganized but mature proliferations of epithelial or mesenchymal tissue in an appropriate anatomic region are termed what?
Hamartomas
94
non neoplastic normal mature tissue aggregates at an ectopic site are called what?
Choristoma
95
which organelle gives the more basophilic appearance to neoplastic cell cytoplasm?
ribosomes
96
which mechanism leads to cellular senescence?
replicative senescence
97
some neoplastic cells undergo permanent replicative senescence in which phase of the cell cycle? which protein mediates this process?
G1 - mediated by p53
98
expression of beta galactosidase by neoplastic cells indicates what?
that they are senescent
99
what is the function of telomerase?
it allows telomeres to be replicated and expanded, prolonging a cells lifespan
100
DNA damage results in apoptosis triggered by which protein?
p53
101
what is the major cellular inhibitor of autophagy?
mTOR
102
what are the three steps in neoplastic transformation?
Initiation, promotion, progression
103
the introduction of an irreversible genetic change into normal cells is which stage of carcinogenesis?
initiation
104
the outgrowth of initiated cells in response to selective stimuli is which stage of carcinogenesis?
promotion
105
are promotors mutagenic of non-mutagenic?
non-mutagenic and usually reversible
106
which stage of carcinogenesis is reversible?
promotion
107
how are retinoids used in cancer therapy?
retinoids are vitamin A derivatives that can induce maturation of some human leukemia cells
108
following initiation and promotion, the result is a tumor which is __________. (Benign or malignant)
Benign
109
which GF is released by tumor cells that have a "schirrous response"
PDGF
110
wihch GF produced by tumor cells stimulates tumor-associated fibroblasts to become myofibroblasts with contractile abilities?
TGF-a
111
down regulation of thrombospondin by tumor cells promotes which process necessary for tumor growth?
angiogenesis
112
which GF is essential for lymphangiogenesis and lymphatic metastasis?
VEGF
113
what is the target for NK cell mediated killing of tumor cells?
stress induced ligand
114
Many tumors produce TGF-a (or TGF-b?) typo in zachary? which has what effect?
inhibits proliferation and function of lymphocytes and macrophages
115
what are three examples of immunosupppresive factors produced by tumor cells?
TGF-a or TGF-b? typo? (inhibits proliferation of lymphocytesa and macrophages), FASL (triggers T cell apoptosis), release of tumor antigens into circulation that complex with antibodies
116
what is the target of the melanoma vaccine?
human tyrosinase protein
117
tumor cell migration is stimulated by which factor?
scatter factor or HGF
118
loss of which molecule is an essential initial step for carcinoma metastasis?
cadherins/catenins
119
what is the funtion of type IV collagenase and urokinase to tumor cells?
degrade the basment membrane to allow for invasion/metastasis
120
cells undergoing EMT have decreased expression of which molecule?
E cadherin
121
most carcinomas metastasize via which route (lymphatics or blood)
lymphatics
122
most sarcomas metastasize via which route (lymphatics or blood)
blood
123
which cytokines are involved in cancer cachexia?
TNF-a, IL-1, IL-6, prostaglandin
124
three neoplasms in dogs that are associated with PTHrp production and hypercalcemia of malignancy?
AGASACA, lymphoma, multiple myeloma
125
how does PTHrp increase blood calcium? Three mechanisms
increases calcium release from bone, increases calcium absorption from intestines, increases calcium resorption in kidneys
126
nodular dermatofibrosis in germal shepherds is due to which renal neoplasm?
bilateral renal cystadenocarcinomas
127
what does mutation fixation mean?
a single point mutation won't necessarily become reproduced unless it is "fixed" in the genome by being used as a template for synthesis of complementary DNA. It requires 1-2 rounds of replication for the muation to become fixed in the genome
128
small deletions in one or two base pairs that cause a shift in the reading frame during protein synthesis are called what?
frameshift mutations
129
the internal tandem duplication of the c-kit gene in canine mast cell tumors is the result of which type of heritable alteration?
genomic amplification
130
trisomy of chromosome 13 is a feature of ~25% of which canine malignancy?
lymphoma
131
early age of onset, formation of bilateral tumors in paired organs, multiple primary tumors in unpaired organs, and a family history of cancer are features of which type of heritable disorder? how does it come about?
Cancer syndrome - resulting from germline mutations in oncogenes or tumor suppressor genes
132
hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in GSDs is an example of which type of heritable change?
germline mutation - cancer syndrome
133
in neoplastic cells, telomere shortening can lead to what change?
genomic instability and reactivation of telomerase
134
hypomethylation leads to gene ___________ where as hypermethylation leads to gene _____________.
Activation, silencing
135
which epigenetic change leads to more relaxed chromatin and DNA that is more accessible to transcription factors?
histone acetylation
136
5' CGP islands (promoter regions) in cancer cells are generally _____methylated.
hypermethylated - generally the promotor region of tumor suppression genes
137
what are some ways in which protooncogenes can become activated (oncogenes)?
1. amplification - a signal to transcribe the gene results in many more copies being produced. 2. mutations that lead to constituitive activation
138
RAS activation leads to signaling through which pathway?
MAPK
139
which protein inactivates RAS in non-neoplastic cells?
GAP (GTPase activating protein)
140
mutated RAS that cannot be inactivated leads to constituitive signaling through which pathway?
MAPK
141
the idea that both alleles of a tumor suppressor gene need to undergo mutation for cancer to develop is called what?
The two hit hypothesis
142
inactivation of only one copy of a tumor suppressor gene that is sufficient for tumor growth is called what?
Haploinsufficiency
143
what are the two major functions of the tumor suppressor gene p53?
cell cycle arest and apoptosis after DNA damage
144
how does p53 activate apoptosis in cells with DNA damage?
BAX
145
enhanced expression of p53 leads to increased transcription of which gene that leads to G1 arrest?
p21
146
which type of DNA repair mechanism is responsible for fixing single nucleotide mismatches?
mismatch repair enzymes; MLH1 and MSH2
147
which type of DNA damage leads to the formation of pyrimidine dimers (a type of DNA adduct)?
UV light
148
how are pyrimiding dimers removed from the DNA?
nucleotide excision repair
149
p53 activation leads to DNA repair mechanism proteins such as?
GADD45
150
APC (which is lost or mutated in human adenomas) is what type of gene?
a tumor suppressor gene
151
what is the difference between direct acting and indirect acting carcinogens?
direct acting do not require conversion, indirect acting do
152
what are complete carcinogens?
carcinogens that are able to initiate and promote tumorigenesis - radiation is an example
153
fes, fgr, abl,kit, fms are all examples of what?
animal derived oncogenes
154
endogenous E6 and E7 are papilloma derived oncogenes that inhibit which tumor suppresor proteins?
E6 inhibits p53, E7 inhibits pRb
155
avian leukosis virus inserts viral DNA in the promotor region of which protoncogene?
c-myc
156
which tick borne disease can give rise to clonal lymphocyte populations?
Ehrlichia
157
Expression of which of the following adhesion molecules may enhance spread of circulating neoplastic cells to lymph nodes?
CD44
158
AKT normally inhibits the production of which protein?
BAD
159
Which cytokines is an important regulator of epithelial-mesenchymal transition and metastasis?
TGF-b
160
Ras pathway involves which type of R?
Tyrosine kinase
161
what prevents uncontrollable RAS activity?
GAPs
162
K-ras mutation seen in which cancers?
Colon, pancreas
163
H-Ras mutation seen in which cancers?
bladder tumors
164
N-ras mutations seen in which cancers?
Hematopoietic tumors
165
PI3K and BRAF are examples of which type of proteins?
signal transducing
166
substrates of AKT signaling protein
mTOR (activated - stimulates lipid and protein synthesis), BAD (inactivated - pro apoptotic), FOXO (inactivated - promotes apoptosis)
167
FeLV integrates into the feline genome at which locus?
C-myc
168
Rb prevents cell cycle progression by complexing with which transcription factor?
E2F
169
Role of ATM
sensor of DNA damage
170
Role of MDM2
Oncoprotein: degrades p53 and inhibits is activity
171
AKT signaling decreases which cell cycle inhibitor to allow for cell cycle progression?
p27 (inhibits cyclin E-CDK2)
172
E-cadherin is part of which pathway?
WNT
173
Loss of PTEN seen in which two canine tumors?
osteosarcoma, histiocytic sarcoma
174
is PTCH a tumor suppressor or oncoprotein?
tumor suppressor in hedgehog signaling pathway
175
proteins encoded on CDKN21 locus
P16/INK4 (blocks Rb phosphorylation) and P14/ARF (inhibits MDM2 and activates p53)
176
MEN-1 involves which three neoplasms
pituitary, parathyroid, pancreas
177
MEN-2 involves which three neoplasms
thyroid, parathyroid, adrenal
178
hydroxylated HIF-1a binds to which protein to promote its ubiquitation and proteosomal degradation when oxygen is present?
VHL
179
which two tumor suppressors oppose the Warburg effect?
PTEN and p53
180
which signaling pathway inhibits autophagy?
PI3K/AKT/mTOR
181
25% of canine lymphomas have trisomy of which chromosome?
13
182
type of RNA important for maturation of rRNA and ribosomal assembly?
snoRNA
183
type of mutation that does not confer a fitness advantage
passenger mutation
184
chemical carcinogens cause what type of DNA damage?
DNA adduct formation
185
type of cKIT mutation in canine MCT?
internal tandem duplication
186
type of mutation in canine transitional cell carcinomas?
missense mutation
