Cancer Flashcards
1
Q
How many gene changes are needed to cause cancer?
A
5/10/15
2
Q
Definition of malignancy?
A
Ability to grow in an alien environment
3
Q
Where do carcinomas often migrate?
A
Lymphatics
4
Q
What specific effects are there from lung tumours?
A
ACTH, ADH
5
Q
What part of the cervix does papilloma virus infect?
A
Columnar to glandular junction
6
Q
Which molecules receive signals from the basement membrane to tell cells to stop dividing in that plane?
A
Integrins
7
Q
Why does clonal evolution occur?
A
Neighbouring cells have the same mutations
8
Q
Which transition does Rb control?
A
G1/S
9
Q
What inactivates Rb?
A
CDK4 and CyclinD1
10
Q
What inhibits CDK4 and CyclinD1?
A
p21 and p16
11
Q
What does E2F control transcription of?
A
S phase genes
12
Q
Which mutations are dominant?
A
Oncogenes
13
Q
Which mutations are recessive?
A
Tumour suppressor
14
Q
How does p53 bind?
A
As a tetramer
15
Q
Which phase does p53 act in?
A
S
16
Q
What stabilises p53?
A
Mutant DNA
17
Q
Which pathway are BRCA1/2 involved in?
A
Homologous repair
18
Q
Which kind of instability does BRCA1/2 result in?
A
Chromosomal
19
Q
Which cancer has mutations in DNA polymerase epsilon?
A
Colon
20
Q
What do microtubule kinetophores monitor?
A
Lagging chromosomes
21
Q
What do microtubule kinetophores inhibit?
A
APC
22
Q
What happens when the lagging chromosomes align?
A
Anaphase promoting complex
23
Q
Which drug selects for resistant cancer?
A
Cis-platin
24
Q
How do cells reactivate BRCA2?
A
Compensatory frameshift mutation
25
Why is APC rare?
Patients die at reproductive age
26
What mutation causes Lynch syndrome?
Mismatch repair gene
27
What do patients get if retinoblastoma does not develop?
Sarcoma
28
What do Wnt receptors inhibit?
APC degradation complex
29
What does APC degradation complex activate?
Beta catenin
30
What does beta catenin activate?
TCF4
31
Where is TCF4 located?
Nucleus
32
What does EGF receptor activate?
Ras, PI3KCA
33
What does the TGF beta receptor activate?
SMADs
34
How do SMADs affect proliferation?
Inhbiit
35
What happens to the TGF receptor II in cancer?
Inactivated
36
How is stem cell compartment expanded in APC?
Wnt pathway activation or knocking out APC
37
What does BAX inhibit?
BCL2
38
How does BAX act?
Dimerises
39
What repeats are in telomeres?
TTAGGG
40
How much do telomeres shorten per cell cycle?
100bp
41
What is TERT?
The telomerase gene
42
What is the most mutated gene in human cancer?
p53
43
Which kinases detect DNA damage?
ATM/ATR
44
Which p protein does p53 activate?
p21
45
Which pathway does p21 inhibit?
Rb pathway
46
What mediates p53 degradation?
mdm2
47
What blocks mdm2?
p14
48
How does glycolysis change in cancer cells?
Upregulates
49
Which Krebs cycle enzyme gets point mutations?
Isocitrate dehydrogenase
50
What does the Krebs cycle produce which interferes with DNA methylation?
Hydroxyglutarate
51
Which cancers have isocitate DH mutations?
Leukaemias and glioblastomas
52
How does site on injection affect metastasis of a tumour cell?
No effect
53
What is the inefficient step in metastasis?
Survival after extravasation
54
Which kind of mutations give cell a selctive advantage?
Driver mutations
55
Which mutations don't affect cancer development?
Passenger mutations
56
What does ERG control?
Differentiation
57
Which genes does MYC turn on?
Cell cycling
58
What do beta-catenin, TCF4, p53, MYC and ERG all control?
Chromatin modification
59
What is MLL?
A histone lysine methyltransferase
60
Which cancers have MLL?
Chromosome translocations in leukaemias
61
Which protein holds epithelial cells together?
E-cadherin
62
How is E-cadherin inactivated?
Methylation of promoter DNA
63
Which sequencing is used to find small scale mutations?
Illumina
64
Which mutations is Illumina good for?
Ras/Raf
65
Which mutations is illumina not good for?
Indels
66
Which chromosomes are involved in CML?
9-22
67
Which technique is used to see amplifications?
FISH
68
What is amplified in glioblastoma?
EGFR
69
What is deleted in glioblastoma?
p16
70
What is measured to see deletions and amplifications?
Copy number
71
Why is B-RAF duplication activating?
Fuses with highly active neighbour gene
72
What kind of receptor is ABL?
Tyrosine kinase
73
What controls the ABL gene?
N-terminal regulatory domain
74
Which kind of cancers have fusion genes?
Epithelial
75
What forms insertions in some tumours?
LINE1 retrotransposons
76
What does a transformation assay show?
Transformation by a transforming oncogene
77
What can be used to remove the tumour suppressor gene between two "lox" genes?
Cre recombinase
78
What does TPA mimic?
DAG
79
What does DAG activate?
PKC
80
What causes a thymidine dimer?
UV light
81
What is the structure of beta naphthylamine?
Aromatic amine
82
What is the structure of dimethyl nitrosamine?
Nitrous acid and amine
83
Where is dimethyl nitrosamine from?
Meat
84
Why does benzopyrene cause cancer if it is inert?
It is activated
85
What do hydratases, P450 monoxygenases, and sugar concentration do?
Increase solubility to aid excretion
86
Which carcinogen does benzopyrene form?
Epoxide
87
Where is beta naphthylamine inactivated?
Liver
88
Why does NMU cause mammary tumours in puberty?
Dividing cells more susceptible
89
Which Aspergillus toxin causes liver toxicity and cancer?
Aflatoxin
90
Which Aristolochiaceae acid causes kidney toxicity, UTUC
Aristolochic acid
91
How is aflatoxin activated?
Oxidation
92
What is aflatoxin activated to?
An epoxide
93
What is the base change in UV light?
C to T
94
What is the base change in smoking?
C to A
95
What base change does aristolochic acid cause?
CT to CA
96
What does the Ames test measure?
Histidine biosynthesis defect
97
What does a high LET track show?
Alpha particle
98
What does a low LET track show?
Gamma wave
99
What is radiation dose measured in?
Grays energy absorbed
100
What is the quality factor for x-rays?
1
101
What is the quality factor for alpha particles?
20
102
How do you work out Sieverts?
Gray x quality factor
103
Which cancers does EBV cause?
Burkitt's lymphoma and nasopharyngeal carcinoma
104
Which cancer does HBV cause?
Hepatocellular carcinoma
105
Which virus causes Kaposi's sarcoma?
HHV8
106
Which virus causes T cell leukaemia or lymphoma?
HTLV1
107
What is the most important treatment in cancer therapy?
Surgery to remove primary tumour
108
What % of testicular cancers does cisplatin cure?
70-90%
109
Which pathways do PARP inhibitors target?
DNA repair
110
How does PARP recruit repair systems?
Binds to strand break and adds ADP-ribose string
111
Why can't PARP inhibitors work at replication forks?
Needs BRCA2
112
What does Glivec bind?
ABL kinase
113
What does Vemurafenib inhibit?
B-RAF
114
What % of patients does vemurafenib work in?
80%
115
How does vemurafenib resistance develop?
Ras amplifications or mutations
116
What are the oncolytic adenoviruses and what do they inactivate?
Onyx-O15 and H101, Rb1 and p53
117
What does E1A inhibit?
RB1
118
What does E1B55k inhibit in engineered adenoviruses?
p53
119
If the E1B55k protein is removed, which are the only cells a cytolytic virus can replicate in?
p53-mutant
120
How does the acquired immune system affect non-viral cancers?
None
121
What could be downregulated to increase cytotoxic T cell killing?
CTLA-4 and PD-1
122
What was the survival increase in patients who has peripheral tolerance downregulated?
11%
123
Which cancers can be treating by peripheral tolerance downregualtion?
Melanoma and lung
124
Which patients have a better response to peripheral tolerance downregulation?
Those with more mutations
125
How many Rb-1 copies must be mutated for cancer?
Both
126
Which chromosome is Rb-1 on?
13
127
Which virus binds and inactivates Rb-1?
HPV
128
Which chromosome are APC/beta-catenin found on?
5
129
How is APC activated?
Preventing degradation by point mutation the domain which degradation machinery bind to
130
What do mutations induce in APC?
Stop codon
131
What is the third change in colorectal cancer?
KRAS/B-ARF
132
What is the commonest mutation in KRAS/B-RAF?
Valine to glutamic acid and position 600
133
What does teh KRAS/B-RAF cause glutamic acid cause activation?
Mimics phosphorylation
134
What is the anti-Ras drug?
None
135
How many K-RAS copies are usually mutated?
Only one
136
How is MLH1 inactivated?
Epigenetic methylation
137
What is the usual mutation in PIK3CA?
Negatively charged amino acid to positively charged
138
Which positions in PIK3CA are missense mutations?
542, 545, 901, 907, 1047
139
What does PTEN reverse the action of?
PIK3CA
140
What does herceptin target?
EGFR and ERBB2
141
How many new insertions do LINE1 retrotransposons form?
10-1000
142
What % of colon cancer have loss of mismatch repair?
15%
143
Most common cause of loss of mismatch repair?
Methylation
144
What happens to promoters at high doses?
Saturates
145
Which protein normally forms dimers or oligomers?
BCR
146
Which pathway signals through Smad4?
TGFbeta
147
What normally happens to Kras?
Point mutation
148
Is p16 oncogene or tumour suppressor?
TSG
149
Is SMAD4 an oncogene or tumour suppressor?
TSG
150
What is cachexia?
Systemic wasting
151
What inhibits CDK4 and CyclinD1?
p16/INK4A
152
How many copies of oncogenes must be mutated?
1 (dominant)
153
How many copies of TSG must be mutated?
Both (recessive)
154
What is a microsatellite?
Shrinkage or expansion of short repeats caused by mismatch repair deficiency
155
What is rate of increase of small mutations in colon cancers which are mismatch repair defective?
100x
156
Which kind of mutations do TGFbetaRII and Bax get?
Frameshifts
157
What is genetic cause of HNPCC/Lynch syndrome?
Mismatch repair defect
158
Which phase does HR operate in?
G2
159
What does BRCA1 do?
Switches on HR
160
What does BRCA2 do?
Prepares single strand ends for base pairing to the other helix
161
Are inherited mutations normally oncogene or TSG?
TSG
162
How many women have a BRCA mutation?
1 in 500
163
What % of spontaneous colon cancer patients have a APC mutation?
80%
164
What is lifetime cancer risk in BRCA1/2?
40-80%
165
What do the Wnts signal by?
Beta-catenin
166
What do AKt kinases act on to inhibit apoptosis?
BAD
167
What is the effect of the TGFbeta pathway on growth?
Inhibitory
168
Which TGFbetaRII components are mutated in colon cancer?
SMAD4 and SMAD2
169
Which kinases does PIP3 activate?
Akt
170
Which cell type does myeloma arise from?
Plasma cells
171
What happens to the crypt region in APC?
Expands
172
How many divisions are usually permitted?
50-100
173
Which viruses inhibit p53?
HPV and adenovirus
174
What mediates oncogene activation of p53?
p14
175
How many cancers have p53 mutation?
1/3
176
Is there a special metastatic subpopulation?
No
177
Two kinds of translocations?
Unbalanced or reciprocal
178
What does CGH hybridisation look for?
Deletion and amplification
179
What kind of protein is RAS?
G protein
180
Which kindof cancers have BRAF mutations?
Melanomas
181
What is the most frequent mutation found in breast cancer?
PIK3CA
182
Which kind of mutations are many APC mutations?
INDELS
183
WHich tumour suppressirs are often deleted?
PTEN and p16/INK4
184
WHich gene is amplified in lung cancer?
MYC
185
What can BRAF be fused to in pediatric brain tumours?
KIAA1549
186
What does the BCR do to the ABL kinase?
N terminus removed to holds it activated in dimers or oligomers
187
Which gene encodes Cyclin D1 and which cancer is it amplidied in?
CCND1, breast
188
What do promoters behave like?
Drugs
189
What does chronic inflammatiom behave like?
A drug
190
Do promoters work alone?
No - only after initiation which causes DNA damage
191
Is cigarette smoke a promoter or initiator?
Both
192
What do people with xeroderma pigmentosum lack?
Excision repair
193
How is beta-napthylamine activated?
Hydroxylation
194
What is added to beta-naohthylamine to make is harmless?
Glucuronic acid
195
What is the most powerful promoter known?
TPA
196
What cannot be tested for in animals?
Promoters
197
Which PV proteins inactivate p53 and/or Rb?
E6 and E7
198
In which areas do people get Burkitt's lymphoma?
Malaria endemic
199
Which enzym does single strand repair require?
PARP
200
What does imatinib bind to?
ATP bindign region in the inactive conformation
201
What is the mutation for imatinib resistance?
Removes hydrogen bonding site for the drug
202
What domain does vemurafenib target?
ATP binding
203
What kind of cancer is vemurafenib used in?
Melanomas
204
How does CTLA-4 downregulate T cells?
Compete with CD28 by binding B7
205
What are the first cancers to respond to immune checkpoint inhibitors?
Most mutations so the highest number of alien peptides
