Cancer 5 Flashcards
1
Q
what is MOI for ataxia telangiectasia
A
AR
2
Q
whre is mutation in ataxia telangiectasia
A
mutation of ATM
one from each parent
3
Q
draw pathway for ATM
A
pg 160
4
Q
what does ATM phosphoryalate
A
kinase that can phoshporylate p53
5
Q
where is mutation for bloom syndrom
A
BLM
6
Q
what does BLM code for
A
DNA helicase
7
Q
what kind of disorder is bloom syndrome
A
chromosome instability
8
Q
what is characteristic of blooms yndrome regarding chromosomes
A
hundred s of sister chromatid exchanges
9
Q
symptoms of bloom
A
sun senstivie
dwarfism
immune dfeicience
etc
10
Q
werner syndrome is caused by mutation in
A
WRN
11
Q
WRN codes for
A
DNA helicase & exonuclease
12
Q
what distinguishes werner syndrome from other chromosome instability disease
A
premature aging
13
Q
premature aging starting at puberty, short stature, cancer is what disease
A
werner syndrome
14
Q
why premature aging in werner syndrome
A
the DNA helicase (that WRN codes for) is involved in telomere maint.
15
Q
fanconi anaemia have mutations where
A
FA complex
16
Q
pancytopenia is
A
bone marrow failure
17
Q
fanconi anaemia are at risk of developing what
A
AML, lymphoma, hepatic carcinoma
18
Q
pancytopenia, skeletal (upper limb) abnormalities is what disease
A
fanconi anaemia
19
Q
Where do FA genes work
A
BRCA pathway
20
Q
what is FA gene important for
A
DNA repair
21
Q
how can viruses cause cancer
A
oncogenic virus expresses oncogene, so viral genes are expressed when go into cell
viral genome insert or integrate into host cell and the insertion could disrupt tumor suppressor or oncogene
22
Q
EBV
A
ebson bar virus
23
Q
EBV (virus) associated with what cancers
A
burkitt lymphoma
B-cell lymphoma
24
Q
B-cell lymphoma is particularilly associated with
A
HIV or pts at low immunity
25
hepatitis B & C virus associated with what cancer
hepatic cancer
26
why do hepatitis B & C cause hepatic cancer
due to the chronic infection
27
HTLV
human t cell leukemia virus
28
HTLV-1 retrovirus is responsible for wht cancer
T-cell leukemia
29
HPV responsible for what cancer
cervical
30
oppostunistic neoplasms that infect because of HIV
```
kaposis sarcoma ( HHV-8)
non-hodgkin lymphoma (EBV)
```
31
whwhere does non-hodgkin lymphoma usually occur
in brain
32
what viruses are directly oncogenic and take opportunity from HIV
HHV-8
| EBV
33
papalloma viruses are responsible for
warts
| cervical cancer starts as a wart
34
hepatitis viruses associated with what kind of cancer
liver cancer
35
EBV associated with
burkitt lypmphoma
36
HPV & Cervical cancer draw pathway
pg 171
37
hpv stands for
human papaloma virus
38
HPV is transmitted
sexual
39
different strains/grades of HPV describe
some are more highly oncogenic than others. so female infected wtith some type could lead to higher risk
40
what are add'l risk factors to HPV to getting cancer
smoking
| oral contraceptives
41
what are high risk strains of HPV
16 18 31 45
42
HPV virus encodes for (how does it work, what is initial step)
viral oncogenes that inhigibt p53 and Rb in cell it infects
43
acetic acid does what (gynecology, if pap smear comes out abnormal)
stain any cell infected with virus white
44
CIN stands for
cervical intraepithelial neoplasia
45
what are steps of CIN
CIN I to II to II to cervical cancer
46
Rb is inhibiting
E2F
47
what does E2F normally transcribe
cyclin E
48
P53 activated it can do what
block cell cycle
induce apoptosis
help repair
49
HPV genome encodes for what
hpv genome encodes for E6 and E7
50
what do E6 and E7 inhibit
p53 and Rb
51
draw out HPV oncogenes E6 and E7 and how they affect p53 and rb
pg 173
52
at later stages of cancer, you will see what
massive cytogenetic changes
| VERY unstable
53
when will you see massive cytogenetic changes
at end of cancer
54
what sequence is repeated at end of chromosome that makes telomere
TTAGGG
55
what is function of telomere
protect end of chromosomes
permit complete replication of chromosomal DNA
regulate chromosomal integrity
regulate life span
keep chromosomal integrity during cell division
56
what does it mean that it protects the ends of chromosome
they form a loop at the end of the linear chromosomes, without that, if they are just straight ends, chrom. will fuse together. so they prevent chrom. from fusing together
57
what does it mean that telomeres regulate chromosomal integrity during cell devision & determine life span
t loop - the loop that forms is protectin chrom. from fusing
| also determines lifespan - only stem cells express telomerase
58
length of telomeres at end of chromosome tells what
number of times particular cell can proliferate
59
telomerase is enzyme tha does what
elongates telomeres
60
telomerase is active in what kind of cell
germ cell and stem cells
61
in cancer what is reactivated regarding telomeres
telomerase
62
without telomerase activity, what happens
once cells replicate certain # of times they die
63
how do telomeres protect against DNA repair mechanisms
loop at end of linear chromosomes, when p53 is activated it would think there was a break and would fuse different chromosomes together, so it prevents repair mechanisms from doing taht
64
each cell division chrom. loses what
10-20 TTAGGG repeats
65
end replication problem
in adult cell the telomere repeats will be lost b/c of end of replication problem b/c most cells do not express telomerase. telomerase only expressed in stem cells that need to keep proliferating (germ cells have telomerase). b/c of end replication problem cell will eventually go to senescence
66
senescent cell
can never again go into cell cycle
67
in germline and embryonic cells how much telomeric repeat at end
15 KB telomeric repeat
68
G0 is what
senescence, inactive stage of cell cycle, it will never be able to replicate again
telomeres are too short
69
what causes G0
telomeres are too short
70
if cell continue proliferating after G0 what happens
DNA damage which should result in cell death
71
having telomeres is a way of protecting what?
| determining what?
ends of chromosomes
| determining the lifespan of a cell
72
what is telomerase
enzyme that contains two components
73
what two components are in telomerase
TERC
| TERT
74
what is TERC
RNA template
75
what is TERT
reverse transcriptase
76
TERC + TERT form
telomerase
77
what is function of TERC
synthesising telomere DNA repeats
78
what is function of TERT
synthesises telomere DNA
by copying the telomere
repeat sequences encoded
in the RNA template
79
describe how telomerase works
RNA component base pairs at end and uses rest of template to insert DNA using the reverse transcriptase capability. it slides along inserting new DNA bases
80
what is required for cancer progression regarding telomerase
reactivation
81
in immortal cancer how much has reactivation of telomeres
90%
82
why is there 90% found for reactivation of telomeres in cancer, what happens to other 10%?
independent pathway of telomere elongation - not fully understood
83
will telomerase activiation initiate tumor formation
no
| but it allows for tumor proliferation
84
what is one protein involved in checkpoint when telomere gets too short
p53
85
inhibition of telomerase as a treatment for cancer
hasn't been very successful.
86
dyskeratosis congenita where is mutation
pt has mutation in telomerase - prematurely shortening telomeres
87
why do chrom. fuse together in dyskeratosis congenita
defect in telomerase, cells that should normally be able to express telomerase (like hematopoetic stem cells) are not expressing it, if checkpoints are bipassed and cell still replicates will end up with chrom. fusion events.
88
pts with defect in telomerase are at risk for devloping what
cancer
89
why do pts with dyskeratosis congenita at risk for developing cancer
telomeric repeats are very short very quickly, sometimes checkpoint is bipassed and keeps going through cycle, chrom. fuse together, the fusion is oncogenic. when chrom. fuse together then the alternative pathway could be activated
90
what does tricentric and dicentric chrom mean
they have fused together
91
what happens from metaphase into anaphase when there are tricentric and dicentric chrom
there is a break - which could disrupt tumor suppressor or proto-oncogene, increased instability which could mean activation of alternative pathway and telomeres become partially restabilized
92
what mutation needs to happen to have pt get cancer due to dyskeratosis congenita or other similar disease
alternative pathway for telomerase needs to be activated
93
what are some symptoms in dyskeratosis congenita
defects in cells that proliferate rapidly, hair teeth, nails, etc
94
if there is failure of checkpoint to go to G0 what could happen
cell continues replicating, can lose T loop, end up with chrom. instability (chrom fusion events)
if telomerase activity is not reactivated, cell could die b/c of all the rearrangements and breakages
if telomerase is reactivated or alternative pathway is activated and cell is stabilized then the cell will go on and the tumor will carry on and more mutations
95
draw out checkpoint failure for telomeres
pg 192
96
what is a dicentric chromosome
fusion of 2 chromosomes
