37 Cancer genetics Flashcards
1
Q
Cancer cells have…
A
- uncontrolled cell division
- an alteration of the cell cycle leading to tumor development
- the ability to metastasize
2
Q
What are the three cell regulation checkpoints
A
- g1/S
- g2/M
- M
3
Q
G1/S checkpoint
A
the cell is monitored for proper cell size and undamaged DNA
4
Q
G2/M checkpoint
A
the cell cycle is paused if needed until the replication and DNA repair are complete
5
Q
M checkpoint
A
the cell is monitored for proper spindle formation and attachment
6
Q
what protein classes work at the cell regulation checkpoints
A
protein kinases
cyclins
7
Q
protein kinases
A
phosphorylate proteins allowing changes in their activity
8
Q
cyclins
A
structural proteins that interact to guide the progression through the cell cycle
9
Q
cdc mutations
A
mutations that can result in errors in the cell division cycle
10
Q
cancer
A
a mass of tissue or cells with an unlimited potential to divide and serve no useful purpose in the body
11
Q
What are the major characteristics of cancer
A
hyperplasia
anaplasia
metastasis
12
Q
hyperpolasia
A
uncontrolled cell division with cells that are immortal and invasive
13
Q
loss of bottom shelf boundary
A
cancer cells with hyperplasia grow and sack on top of other cells and will downward into other tissues
allows them to invade body systems and kill good cells by robbing healthy tissue of nutrients
14
Q
anaplasia
A
the structure and function of the cancer cells is undifferentiated compared to normal cells within the same tissue
15
Q
metastasis
A
the ability to move to and establish tumors at other sites in the body
16
Q
tumor
A
distinct mass of abnormal cells that do not have normal controls on cell division
17
Q
benign
A
abnormal cells remain localized and do not invade surrounding tissue
18
Q
malignant
A
cancer cells invade surrounding tissue
19
Q
metastatic tumors
A
occur when cancer cells spread and establish secondary tumors in other sites in the body
20
Q
genetic causes of cancer
A
- single gene
- polygenic
- chromosome aberration
- mutations in somatic cell or in gamete producing cell
- viruses
21
Q
environmental agents of cancer
A
carcinogens cause…
mutations
alteration in gene expression
ex. asbestos, lead, x-rays, UV light, tobacco chemicals
22
Q
what does it mean that cancer is a multi-hit disease
A
several things go wrong over time and eventually a cancerous condition occurs
23
Q
How is cancer a multi-hit disease
A
- most are sporadic and influenced by environment
- they develop over time
24
Q
example of how cancers are sporadic and influenced by the environment
A
- siblings are rarely affected by the same cancer
- populations that migrate to new regions tend to get cancer rates typical of that region
25
example of how cancers develop over time
incidence rises with age
26
High incidence of cancer correlate with...
tissues that undergo more cell divisions as many mutations are due to errors in replication
27
tumor suppressor genes
prevent bad cells from dividing
28
proto-oncogenes
allow good cells to divide
29
loss of function in...
tumor suppressor gene
| can no longer prevent bad cells form dividing leading to a tumor
30
gain of function in...
proto-oncogene
| converts to an oncogene that is always on leading to inappropriate cell division and tumor development
31
oncogene
mutated proto-oncogene
32
compared to breaks of car
tumor suppressor gene
33
compared to gas of care
oncogenes
34
loss of function
complete or partial absence of protein function
recessive-acting mutation - needs mutation in both copies of gene to knock out protein function
35
gain of function
cell produces protein that is not normally present - either new gene product or gene product at new location or inappropriate time
normally dominant-acting mutation
36
example of gain of function mutation
mutation in gene that encodes a receptor for a growth factor might cause mutated receptor to stimulate growth in the absence of the growth factor leading to growth at the wrong time or place
37
about ___% of cancer causing genes are...
tumor suppressor genes
38
describe recessive nature of tumor suppressor gene
the normal alleles produce factors that inhibit division
| if both alleles are mutant, the bad cells are not prevented form dividing
39
APC
tumor suppressor gene involved in colorectal cancer
40
BRCA1
tumor suppressor genes
| important in some breast and ovarian cancers
41
P53
tumor suppressor gene
| involved in many types of cancer
42
RB
tumor suppressor gene
implicated in various cancers
was first correlated with retinoblastoma
43
list some tumor suppressor gene
APC
BRCA1
P53
RB
44
Knudson's two hit hypothesis
hypothesis for the action of tumor suppressor gene based on studies of the RB gene
proposes that both copies need to be defective in the same cell to allow the tumor to develop
45
RB protein
responsible for regulation at the G1/S checkpoint and regulates the action of a transcription factor
46
Knudson's two hit hypothesis and sporadic cancers
two mutations must occur in the same cell to lead to tumor formations
47
Knudson's two hit hypothesis and familial cancers
start with one mutated copy, only need one more mutation in same cell to lead to tumor formation
48
BRCA1 and BRCA2 action
used to repair double strand breaks
when not functioning, broken DNA does not get repaired leading to mutations - these then divide and cause tumors
49
P53
a tumor suppressor gene located on chromosome 17
functions at G1 checkpoint
50
mutations of P53 can be found in...
- colon, lung, breast, brain cancer
| - found in altered form in 50% of human tumors
51
fork in the road
action of p53 determines whether a damage cell is paused until repairs can be made or whether the damaged cell is too badly damaged to repair leading to apoptosis
52
if p53 isn't working properly...
cell division occurs even though the DNA is damaged and the cell division occurs in an unregulated manner
53
p53 response to small DNA damage
p53 is activated, it is a DNA binding protein and can stimulate transcription of p21 which stops the cell cycle
54
p53 response to lots of DNA damage
pt53 stimulations transcription of bcl2 which leads to apoptosis
55
haploinsufficiency
a high susceptibility to cancer occurs when only one copy of the normal allele is present
a diploid organism has loss of function of one copy leaving only one functional copy which does not produce enough of the gene product to exhibit the wild-type phenotype
individuals can still be affected even if the have one normal allele
56
example of haploinsufficiency
bloom syndrome
57
bloom syndrome
- due to defective DNA helicase important in repairing ds DNA breaks
- individuals homozygous for mutated BLM have high rate of cancer
- heterozygous have elevated risk of colon cancer
58
How is bloom syndrome an example of haploinsuffiency
the heterozygote may never develop a mutation in the other copy. However, just the one copy leads not some nonfunctional helicase, leading to increased mutations
59
example of oncogene
myc
60
Burkitt's lymphoma
abnormal B cell function
61
c-myc
ongogene
normally present near end of chromosome #8
normally an antibody producing gene is near chromosome #14
translocation between the two places c-myc near enhancer for the antibody producing gene, leading to high function of c-myc gene resulting in tumors and Burkitt's lymphoma
62
Burkitt's lymphoma is due to a ___ that puts an ___ next to ___
reciprocal translocation
enhancer
c-myc oncogene
63
chronic myelogenous leukemia
fatal, uncontrolled replication of myeloid stem cells
results form reciprocal transloation of c-ABL gene and BCR gene
64
Philadelphia chromosome
translocated cABL and BCR gene leading to CML
65
CML involves chromosomes...
9 and 22
66
Burkitt's lymphoma involve chromosomes...
8 and 14
67
the Philadelphia chromosome produces...
a fusion protein that affects cell cycle control leading to cancer associated with WBCs
68
retroviruses
can cause cancer
they have RNA which they can convert into DNA which then integrates into host cell's DNA
69
HPV is associated with
cervical
penile
vulvar cancers
70
Retroviruses can cause cancer by...
- mutating and rearranging proto-oncogenes
| - inserting strong promoter near proto-oncogenes
71
strong promoters...
often in viruses
| cause genes near the site of virus integration to be overexpressed
72
what happens if a strong promoter is near a proto-oncogene
can overstimulate over-expression of the gene causing it to function as an abnormal oncogene
73
HPV produces...
proteins that inactive p53 and RB allowing cells to overproliferate
74
paladin gene codes for...
a cytoskeleton protein that is important in maintaining cell shape
implicated in metastasis
75
cells that metastasize generally have...
poor cytoskeleton structure allowing them to easily detach from the tumor mass
76
paladin gene was found in a family with a high frequency of...
pancreatic cancer
77
colon cancer involves mutations in the...
APC gene, p53, ras and other
there is a progression from benign adenomas to malignant tumors to metastasis
78
genetic testing of what gene is important to colon cancer
APC - a tumor suppressor gene
79
clonal evolution
over time, tumor cells acquire more mutations that allow them to be progressively more aggressive in proliferation
80
clonal evolution involves mutations that can affect...
- cell cycle regulation
- signal transduction
- DNA repair
- telomere length
- chromosome segregation
- vascularization
81
signal transduction
external signal triggers a cascade of intracellular reactions to produce a specific response
ex. Ras signal-transduction
82
Ras signal-transduction pathway
ras protein can be inactive or active to either allow or not allow external stimuli to start the cascade of events in the cell
if activated leads to MAP kinase activation which activates TF that stimulate genes leading to cell division
83
mutation in ras pathway
the genes that code for Ras proteins are often oncogenes
mutations normally cause it to be stuck in active form leading to cell division
84
repair mechanism in xeroderma pigmentosum
defective nucleotide excision repair
85
defective mismatch repair
implicated in colorectal, endometrial, and stomach cancers
86
defective double strand break repair
implicated in BRCA1 and BRCA2
87
role of telomere length in cancer
- normally telomeres shorten with age leading to cell death
- telomerase works in germline but not somatic cells allowing somatic cells to die and be replaced
- tumor cells often have telomerase expressed to give them "immortality"
88
angiogenesis
growthof new blood vessels - important to tumor progression
growth factor and proteins involved are often overexpressed in tumor cells
inibitors may be inactivated or underexpressed
thought that prevention of this may fight cancer by decreasing metastasis
89
classic cancer model
unregulated growth is due to a serial acquisition of genetic events leading to the expression of genes that promote cell proliferation while silencing the growth of inhibitory genes and blunting cell death
90
cancer is a...
proliferative disease
91
cancer therapy focuses on...
trying to shrink or destroy the tumors
92
genes that can be tested
BRCA1 and 2
P53
APC
RB
93
steps to decrease cancer risk
- HPV vaccine
- avoid environmental factors leading to cancer
- get recommend screenings
94
screenings for breast cancer
regular breast exams
| mammograms
95
screenings for colon cancer
colonoscopies
96
screenings for prostate cancer
PSA test
