Cancer Flashcards

1
Q

The six hallmarks allow a cell to be transformed into what type of cancer?

A

Invasive

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2
Q

Gain of function mutations are typically what?

A

dominant

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3
Q

HER is a receptor for what?

A

epidermal growth factor

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4
Q

Does the HER2 family of receptors function as homodimers or heterodimers?

A

either

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5
Q

HER1 or ErbB1 refer to what?

A

EGFR

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6
Q

How is ErbB1 converted into a constitutively active form?

A

mutation removes ligand binding domain that results in activation

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7
Q

How is HER2 converted into a constitutively active form?

A

a point mutation in TMSR that allows for receptor dimerization

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8
Q

Pancreatic cancers often feature what type of cell signaling mutation?

A

Ras mutations

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9
Q

Burkitt’s Lymphoma results from inappropriate activity of what cell signaling molecule?

A

c-Myc

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10
Q

What type of translocation happens to c-Myc in Burkitt’s Lymphoma?

A

chromosome 8 to chromosome 14

c-Myc near antibody heavy chains

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11
Q

When does this translocation occur?

A

during maturation of antibody producing B-cells

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12
Q

Are mutations in tumor suppressor genes typically dominant or recessive?

A

recessive

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13
Q

What proteins must be liberated from Rb in order to induce cell cycle progression?

A

E2F

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14
Q

What protein is p53 generally associated with? What will this do?

A

MDM2

act as an E3 ubiquitin ligase

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15
Q

What proteins can phosphorylate p53? What will this do to the association of p53 with mdm2?

A

ATM or ATR

cause dissociation of p53 from mdm2

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16
Q

What is a key protein upregulated by p53?

A

p21-CIP1

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17
Q

What is the function of p21-CIP1?

A

cell cycle arrest

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18
Q

If there is too much DNA damage to overcome, what can p53 do to cell growth?

A

signal senescence or apoptosis

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19
Q

What complex is the active form of p53 in?

A

homotetramer

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20
Q

Li Fraumeni patients have a mutant allele for what what gene? This disrupts the formation of what?

A

TP53

TP53 tetramer

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21
Q

What two proteins do the HPV produce?

A

E6 and E7

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22
Q

What is the function of E6?

A

inhibits p53

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23
Q

What is the function of E7?

A

inhibits Rb

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24
Q

Neurofibromatosis occurs due to loss of what gene?

A

NF1

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25
NF1 gene encodes what protein?
neurofibromin
26
What is the function of neurofibromin?
to accelerate the rate at which Ras hydrolyzes GTP
27
Development of neurofibromatosis follows what kind of mechanism?
two-hit
28
What is the role of BRCA2?
homologous recombination
29
Both BRCA1 and BRCA2 are important in the repair of what?
double-stranded DNA breaks
30
Other than homologous recombination, what else is BRCA1 involved in?
G1/2 and G2/M checkpoint
31
Regarding homologous recombination, what do the roles of BRCA1 and BRCA2 appear to be?
delivery of effector proteins to sites of double-stranded DNA breaks
32
What other function does BRCA1 possess?
E3 ubiquitin ligase
33
What does methylation of a gene do?
makes it transcriptionally silent
34
What is the sequence of telomeres?
TTAGGG
35
Short telomeres appear to be recognized as what?
double-stranded DNA breaks
36
Cells implicated in a breakage/fusion/bridge cycle tend to up-regulate what protein?
telomerase
37
What is an important signal relating to sustained angiogenesis?
hypoxia
38
Hypoxia stimulates an oxygen sensitive txn factor known as?
HIF-1ab
39
During normoxia, how is HIF-1ab regulated?
hydroxylated by a proline hydroxylase
40
How do the hydroxylated prolines of HIF-1ab serve to control its regulation?
serve to recruit E3 ubiquitin ligase
41
What happens to these hydroxylated residues during anoxia? What does this entail?
the residues are not hydroxylated HIF-1ab is not targeted for degradation
42
How does HIF promote angiogenesis?
HIF-1a and HIF-1b for a dimer and activate VEGF
43
What proteins normally hold epithelial cells together?
E-Cadherin
44
What two steps must a cell accomplish to successfully metastisize?
tissue invasion and extravasation
45
What product, secreted by tumor cells, breaks down the basement membrane?
matrix metalloproteases
46
What is intravasation?
tumor cell entering the bloodstream
47
What degradation components of the basement membrane signal migration?
collagen IV and laminin
48
What is extravasation?
exit from the bloodstream
49
What is an adenoma?
benign tumor
50
What is a carcinoma?
malignant tumor
51
Patients with FAP develop what kind of colon cancer?
thousands of adenomatous polyps
52
FAP results from mutation of what gene?
adenomatous polyposis coli (APC)
53
beta-catenin stimulates the txn of what two genes?
cyclin D and Myc
54
When WNT binds to its ligand, what happens to beta-catenin?
it is liberated from proteasomal degradation
55
In the absence of WNT ligand, what happens to beta-catenin?
beta-catenin is targeted for proteasomal degradation
56
How do mutations in APC affect WNT signaling?
WNT signaling is constitutively active
57
What is the role of APC regarding WNT and beta-catenin?
to form a destruction complex between APC/WNT/beta-catenin
58
HNPCC patients have defects in what pathway?
DNA mismatch repair
59
What two genes are involved in the mismatch repair defects in HNPCC patients?
MSH2 and MLH1
60
What is the function of MSH2?
to identify mismatch repairs
61
What is the function of MLH1?
to fix the mismatch repairs
62
What chromosomes are involved in the Philadelphia Chromosome? What genes are affected?
9 and 22 BCR and ABL1
63
What product does the ABL1 gene encode?
soluble protein tyrosine kinase
64
What condition features a the philadelphia chromosome?
chronic myeloid leukemia
65
What drug is used to treat chronic myeloid leukemia?
imatinib (Gleevec)
66
What are two additional Bcr-Abl drugs used to treat chronic myeloid leukemia?
nilotinib and dasatinib
67
How do imanitib, nilotinib and dasabitib function?
Bcl-Abl tyrosine kinase inhibitor
68
What is HER2/Neu?
receptor tyrosine kinase
69
What type of receptor is the EGFR? What is another name for this receptor?
receptor tyrosine kinase ErbB1
70
What mutations occurs to make ErbB1 constitutively active?
mutation that removes extracellular ligand binding domain
71
What is the mutation that renders HER2 active?
point mutation that causes dimerization/autophosphorylation in the absence of ligand
72
What cyclins do c-Fos and c-Myc stimulate production of?
Mid and Late phase G1
73
Burkitt's Lymphoma results from inappropriate activitity of what protein?
Myc
74
What type of mutation takes place in Burkitt's Lymphoma? What does this do to Myc?
translocation increase in expression of Myc
75
What chromosomes are involved in Burkitt's Lymphoma?
8 and 14
76
The active form of p53 resides in what sort of complex?
homotetramer
77
Li-Fraumeni patients have a mutated copy of what gene? What does this cause to the protein product?
TP53 inability to form homotetramer
78
What are the apparent functions of BRCA1 and BRCA2 regarding double stranded breaks?
to deliver effector proteins to heal double-stranded breaks
79
What is the sequence of telomeres?
TTAGGG
80
Telomeres prevent shortening of what strand, the lagging or the leading strand?
lagging
81
Short telomeres are detected as what?
double-stranded DNA breaks
82
The lack of telomeres allows fusion of what?
sister chromatids
83
What is the function of E-cadherins?
hold epithelial cells together
84
FAP results from a mutation in what gene?
adenomatous polyposis coli
85
Where do Lynch syndrome mutations appear to congregate?
Microsatellite Repeats
86
What is microsatellite instability?
defective mismatch repair mutations leads
87
What protein that is involved in regulation of cell growth contains microsatellite repeats?
Bax
88
What is the protein product of ABL1?
soluble protein tyrosine kinase
89
What is rituximab used to treat?
non-Hodgkins Lymphoma
90
What chromosomes are involved in Burkitt's Lymphoma?
8 and 14
91
What DNA binding protein is implicated in Burkitt's Lymphoma?
Myc
92
What promoter does Myc aberrantly use in Burkitt's Lymphoma?
antibody heavy chain
93
What protein is dissociated from p53 upon its dissociation?
Mdm2
94
Active p53 is in what kind of complex?
homotetramer
95
How does LiFraumeni disrupt function of p53?
inhibits formation of tetramer
96
BRCA1 and BRCA2 are implicated in what DNA repair mechanism?
homologous recombination
97
Homologous recombination is involved in fixing what type of DNA breaks?
double-stranded
98
Short telomeres are recognized as what?
DNA double-stranded breaks
99
What are two components of basement degradation? What do these proteins doe regarding metastasis?
collagen IV and laminin promote metastasis
100
Activation of WNT pathway results in the production of what two mitogenic proteins?
Myc and cyclin D
101
FAP patients often possess an oncogenic form of what cellular protein?
Ras
102
HNPCC defects occur in what kind of repeats?
microsatellite repeats