Cancer 2 Flashcards
1
Q
name some common causes of cancer
A
inherited cancers chromosome aberrations chemical carcinogens diet ionizing radiation oncogenic viruses
2
Q
describe how viruses can cause cancer
A
when virus affects host cell ,some viruses express viral oncogenes. they inhiit the host cells tumor suppressor genes
some viruses can undergo insertional event, it inserts into host cell genome which could disrupt tumor supresser gene or oncogene
3
Q
inherited cancer
A
pt inherits mutation that directly causes a type of cancer
4
Q
direct inherited cancer
A
if pt inherits mutation in gene, that gene mutation is responsible for onset of that type of cancer
includes hereditary cancer
5
Q
indirect inherited cancer
A
chromsoome instability syndrome
pts inherit mutations → chromosomal instability, that causes mutations which causes cancer
6
Q
what is an example of an indirect inherited cancer
A
xeroderma pigmentosum
they can’t repair UV light, susceptible to skin cancer
7
Q
aquired chromosome rearrangements, what is most common example
A
philadelphia chromosome
8
Q
philadephia chromosome is caused by what
A
translocated chromosome b/w chromosm 9 & 22
9
Q
what is the philadelphia chromosome
A
22q- caused by translocation of chrom. 9 & 22
10
Q
abelson (ABL)
A
intracellular tyrosine kinase
11
Q
what is abelson normally involved in
A
normally involved in transducing signaling
12
Q
what happens as result of t(9:22)
A
transcribe fusion gene encoding for brand new fusion protein
contains exons for BCR & ABL which has constitutevely active tyrosine kinase activity
13
Q
translocations are mostly involved in what kind of cancer
A
leukemias & lymphomas
14
Q
deletion in 1p is commonly found in what ancer
A
colorectal
15
Q
if there are deletions that cause cancer, what kind of gene was most likely located in it
A
tumor supressor
16
Q
chemical carcinogenesis
A
multistep process involving many genes
target: oncogene & tumor suppressor gene
17
Q
what is first step in chemical carcinogenesis
A
initiation: change in DNA 9mutation
18
Q
what is 2nd step in chemical carcinogenesis
A
promotion- clonal expansion
19
Q
what is 3rd step chemical carcinogenesis
A
progression - cells aquiring more and more mutations
20
Q
how is DNA damage a form of cancer treatment
A
cancer cells very susceptible for DNA damage, so most cancer cells killed
21
Q
UV radiation causes formation of what
A
thymine dimers - if not exised, abnormal cross linking b/w bases and breakage of DNA
22
Q
alkylating agens
A
attach alkyl group to base
23
Q
chemical crosslinking
A
aka aduct formation
chemical group prevent attachment to base
24
Q
in alkylation and chemical crosslinking, as a result of covlalent attachemnt, what happens
A
the are no longer guanines, so abnormal cross inking, strand breakage
25
direct acting carcinogen
chemical is directly alkylating or forming aduct in DNA
26
indirect carcinogen
metabolized before reacting with DNA
27
ex of indirect carcinogen
benzo-a-prene (in tobacco smoke)
28
what is an example of what is involved in most lung cancer
smoking
29
smoking causes what percent of cancer death
1/3
30
onset of sporadic cancer is over age of
45
31
if sporadic cancer is under age of 45 assume its
hereditary
32
describe why people in eastern china have such a high rate of dying of liver cancer by age 45
aspergillus flavus mold makes toxin aflatoxin B1
| people eat the mold and toxin and the toxin is converted into reactive hepoxide and induces changes in genome
33
in cigarette smoke benzo-apyrene is converted to what
BPDE
34
how much of cancer could be prevented by healthy diet and healthy weight
30-40%
35
obesity is strongly linked to what kind of cancer
GIT, breast, prostate, cervix, uterus
36
low fiber, high glycemic index is associated with what cancer
GIT cancer
37
radiation results in what
breakage of genome, which could cause cancer
38
viruses associated with how many tumors
10-20%
39
when cell is transofmred, what does it mean
initiated to start proliferating
40
EBV
(Epstein–Barr virus)virus can cause burkitts lymphoma - usually found in mandble
41
HTLV stands for what
human t cell lymphema virus
42
HTLV results in what
t cell leukemia
43
HIV infection and cancer
aids - immuno supression which could result in infection of opportunistic virus
44
HPV linked to what cacner
cervical
45
HPV is what kind of virus
DNA virus
46
when HPV infects what does it do
contains oncogenes E6 & E7 which inactive p53 and Rb (tumor suppressors)
47
helicobacter pylori is konwn to be associated with what
gastric cancer
48
why does helicobacter pylori cause gastric cancer
chronic inflammation
49
describe how tumor progression is a multistep process
Summary: selection of cells with progressive capability for proliferation, invasion & metastasis
after each step, a cell could aquire another mutation that has a selective advantage, and it proliferates even more rapidly
50
CIN stands for what
cervical intraepithelial neuroplasia
51
APC stands for what
adenomatic polyposis coli
52
what are the intermediate stages of cancer induction
polyps, benign adenomas, carcinomas can be isolated
53
beinign tumor becomes more and more aggressive until
it eventually metastisized
54
how can physical examination diagnose cancer
location & size, regional lymphadenopathy
| brain tumor - neurological symptoms
55
regional enlarge lymph nodes
if they are hard and non tender, suggest spread of cancer
| if they are not hard, suggestive of infection
56
general symptoms of cancer
unexplained weight loss, cachexia, lethargy, anorexia, nausea, confusion
fever, night sweats, infection, bruising
fatigue, anaemia, urogenital bleeed
57
what is cachexia
tissue wasting, occurs in late stage of cacner
58
hypercalcaemia suggests tumor has spread where
suggests cancer has spread to bone
59
hypercalcamia?
high calcium level in blood
60
why do pts with leukemia & lymphoma have high amounts of infection?
bone marrow taken over by cancerous cells, so can't produce enough normal cells
pt is anemic (not enough RBC)
recent infections (not enough WBC)
61
PSA test can test for what cancer
prostate
62
CA125 test can test for what
ovary
63
CEA can test for what cancer
colon & lung (blood tests)
64
what radiology tests can be used to detect cancer
xray, ct ,mri pet
65
cancer is a ____ process
multistep
66
cancer is a ____ ____ nomatter what the cause
genetic disease
67
most cancers are ____, some are inherited
sporadic
68
within sporadic cancers, some pts have inherited predisposition. so if first degree relatives are affected, could have
inherited predisposition
69
mendelian cancer
inherited with mendialan, the cancer causing mutation is in every call of body
70
sporadic cancer is ____
multifactoral
71
go through multistep process
slide 54
72
cancer is clonal & heterogeneous
but not all daughter cells surivive, some won't have mutations combatible with life
73
eventually mutations will result in disruption of
chromosome
74
disruption of chromosomes leads to what in cacner
more mutations and more cancer
75
what are two examples of caretaker genes
MSH2 & MLH1
76
what are two major genetic changes that happen in cacner
activation of proto-oncogene
| loss of function of tumor supressor genes
77
are apoptosis genes always included in tumor suppressor and oncogene categories
sometimes genes that cause apoptosis are put in with tumor supressor and oncogene ,sometimes they aren't
78
activation of what kind of gene in cancer regarding cell death
activation of anti-apoptotic gene
79
anti-apoptotic gene is type o fwhat
proto-oncogene
80
proapoptotic gene is a type of what
tumor supressor gene
81
cancer has loss of what gene regarding apoptosis
loss of proapoptotic gene expression
82
caretakers do what
monitor genome & repair it
| they make sure mutations are fixed
83
what kind of mutation happens to tumor suppressor gene to cause cancer
loss of function mutation
84
how many mutations need to to occur to have loss of function of tumor suppressor gene
2 mutations
85
what specifically has to happen for true loss of functio of tumor suppressor gene
both alleles of same tumor suppressor have to be lost
86
what kind of mutation results in proto-oncogene
gain of function mutation
87
how many mutations have to occur to have proto-oncogene
1 mutation
88
1 loss of function in 53 and 1 loss of function of RB - affect on cell?
no affect
89
single mutation of proto-oncogene results in what
oncogene - promotes proliferation
90
proto-oncogene is what
any gene that normally simtulates cell proliferation
91
a point mutation in proto-oncogene can potentially do what
activate it
92
mutation in promoter region of proto-oncogene
drives increased expression of w.t. gene.
93
if there is overexpression, even if it is w.t, it is:
oncogenic change
94
both gene amplification and regulatory sequence mutation resutls in what
overexpression of wild type
95
what two things can happen with chromosome translocation regarding oncogene activation
over-expression: promoter region from different gene that joins to the chromosome, that promoter region is now controlling the proto-oncogene of the other genes promoter. the new promoter is a lot stronger, so increased protein expression
chimeric gene product: like philadelphia chromosome - it's always switched on, brand new protein produced that is hyperactive
96
mutation in promoter region, gene amplification, or translocation, in all of it there is what
overexpression
97
draw out oncogene mechanism chart
pg 64
98
anythng that normally simtulates proliferation is a
proto-oncogene
| b/c if they are activated - excessive proliferation
99
what are two examples of hereditary cancer via oncogene activation
Multiple endocrine neoplasia type 2 (MEN2)
Hereditary papillary renal carcinoma
100
why are oncogene activation hereditary cancer rare
not usually compatible with survival
101
MEN2 stands for what
Multiple endocrine neoplasia type 2
102
pts with hereditory oncogene cancer usually present with cancer when
early in life
103
pts with MEN2 are at risk for developing what
pheochromocytoma
104
what are two types of MEN2
MEN2 A
| MEN2B
105
MEN2 have gain of function utation where
RET (can echo, i think she talked abou tmroe)
106
what change is frequently found in MEN2 who develop tumors
1p loss
107
What is summary of MEN2
they have gain of function but it is not sufficient to form tumors, add'l mutations are needed
108
MET is what
hepatocyte growth factor receptor
109
in hereditary papillary renal carcinoma, where is mutation
MET (HGFR) mutation
110
inherited mutation in MET results in risk of developing what cacner
renal carcinomas
111
growth factors normally involved in stimulating proliferation/survival are all what
proto-oncogens
112
```
PDGF/PDGFR
FGF/FGFR
HGFR (MET)
RET (RTK)
VEGF
EGFR
HER2
are all examples of what
```
growth factor - proto-oncogene. they are all commonly found activated in cancer
113
RAS is what kind of protein
signal transducing protein (GTPase)
114
Signal transducing proteins
RAS (GTPase)
Non-receptor TKs
ABL
Transcription factors
MYC
JUN, FOS
are all what
proto-oncogenes, can be activated in different ways
115
RAS activation
found activated in a ton of cancers
found in 90% of pancreatic cancers
50% colon
116
RAS is bound to what
GDP
117
when RAS bound to GDP it is
inactive
118
When RAS bound to GTP it is
active
119
when RAS is active what does it do
activates GEF
120
if RAS is active, what will it do
just keep activating GEF and other kinases
121
MYC is
TF that is activated at end of RAS pathway
122
MYC - targetgene?
cyclin D
123
if MYC is switched on it results in
tumor formation
124
What cancers do you often find MYC activation in
burkitt lymphoma
| breast, colon, lung
125
burkitt lymphoma and follicular lymphoma are examples of what
overexpression of w.t. proto-oncogene
126
Burkitt lymphoma is translocation b/w which chromosome
8 & 14
127
as a result of 8 & 14 translocation
overexpression
128
resulting chromosome that contains original centromere from chrom 8 is what
der 8
129
der 14 has which centromere
original centromere from chromosome 14
130
chrom. 8 has what gene sequence
MYC
131
chrom. 14 has what gene
IGH
132
how is translocation of chrom 8& 14 aquired
they are all acquired translocation. as soon as cell aquires it, it overexpresses MYC, so cell proliferates rapidly.
133
What are the four stages of progression of cancer development in uterine cervical epithelium
1. normal stratified squamous epithelium
2. low grade CIN
3. high grade CIN
4. malignancy
134
t(8;14) is what cancer?
burkitt lymphoma
135
t(14;18) is what cancer?
follicular lymphoma
136
t(9;22) is what cancer?
chronic myeloid leukemia
137
t(15;17) is what cancer?
acute promyelocytic leukemia
138
t(11;22) is what cancer?
ewing sarcoma
139
which two types of cancer from translocations lead to over-expression of proto-oncogene?
burkitt lymphoma
| follicular lymphoma
140
which three types of cancer from translcoations create fusion/chimeric gene?
Chronic myeloid leukaemia
Acute promyelocytic leukaemia
Ewing Sarcoma
141
which gene is affected that leads to over-expression of proto-oncogene in burkitt lymphoma?
MYC
142
which gene is affected that leads to over-expression of proto-oncogene in follicular ymphoma?
BCL2
143
fever, night sweats, infection & bruising are symptoms of what
leukemia & lymphoma
