Lecture 38 Genetics of Cancer oncogenes and Tumor Suppressors Flashcards
1
Q
What does chromosomal translocation lead to?
A
- production of protein product that shouldn’t exist
2
Q
What is a chronic mylogenous leukemia?
A
- bone marrow produces excessive amounts of abnormal granulocytes at the expense of other healthy white blood cells.
3
Q
Why was Philadelphia chromosome named as such?
A
- because it was discovered in a Philadelphia lab
4
Q
When we extract DNA from blood where do we get it from?
A
- white blood cells because RBC’s don’t have a nucleus
5
Q
Is a single mutation enough to cause cancer?
A
- no you need a second hit
6
Q
Is cancer or tumor formation somatic?
A
- yes it is a somatic event involving other mutations and environmental factors
7
Q
Do most inherited mutations associated with cancer affect a persons risk for developing cancer?
A
- Yes
8
Q
Does tumor growth start with multiple cells?
A
- no it starts with a single cell
- tumor growth and progression generally involves multiple, successive rounds of genetic changes with the end result of natural selection of a clonal cell that produces a tumor or cancer
9
Q
Do tumors only arise from an increase in cell division?
A
- no they can arise from decreased cell apoptosis
10
Q
Can you develop a tumor while having normal cell division?
A
- yes if the cell is not having normal apoptosis
11
Q
A tumor resulting from genetic gene inactivation would come from?
A
- a nucleotide change
12
Q
What is an epigenetic change that leads to tumors?
A
- a change outside of DNA sequence that regulates the gene
- such as an inhibitor being eleminated
13
Q
Do common variants of a single nucleotide have a high risk of cancer?
A
- no they have a low risk
14
Q
Do mutations in the BRCA1/BRCA2 that are rare variants and high penetrance increase risk of cancer?
A
- yes
15
Q
What type of cancer has BRCA1/BRCA2 been linked to?
A
- many types
- breast
- ovarian
- lymphatic
16
Q
What are malignant tumors classified by?
A
- their cell type from which they originated
17
Q
Carcinomas come from what type of tissue?
A
- epithelial cells
18
Q
Sarcomas arise from what type of tissue?
A
- connective tissue or muscle cells
19
Q
Leukemia’s derive from ___ blood cells and their precursors?
A
- white blood cells
20
Q
What are the precursors of white blood cells?
A
- hematopoietic cells
21
Q
Where do lymphomas derive from?
A
- lymphatic tissue
22
Q
Where do gliomas derive from?
A
- glial cells in the CNS
23
Q
What are adenomas?
A
- benign epithelial tumors with glandular organization
24
Q
What are chondromas?
A
- benign tumors that arise from cartilage
25
What is a characteristic of benign tumors?
- they are contained within the tissue where they originated
26
How can you differenciate a malignant tumor from a benign?
- a malignant tumor develops invasiveness and can grow to distal sites outside of the tissue where it originated from
27
Is a high grade intraepithelial neoplasia benign or malignant?
- it is still considered benign because it has not escaped the original tissue
28
What type of cancer can tobacco lead to?
- lung, kidney and bladder
29
What type of cancer can a diet low in vegetables and high in salt lead to?
- stomach
| - esophagous
30
What type of cancer can a high fat low fiber, fried and broiled food diet lead to?
- bowel
- pancreas
- prostate
- breast
31
What can alcohol and tobacco lead to?
- throat and mouth cancer
32
Why do chemotherapy and other cancer treatment target stem cells?
- because stem cells grow very slow but they produce progeny that produce tumors
- chemo is trying to eliminate stem cells
33
What do mutations to a transit amplifying cell or normal cell lead to?
- a malignant cancer stem cell that continues to grow and produce other cancer cells
34
Can tumors live without a blood supply?
- no they need angiogenesis to grow and that is why they produce VEGF
- they are very self sufficient
35
Do external anti proliferative signals effect cancer cells?
- no they are resistant to anti growth signals
36
Are cancer cells prone to apoptosis?
- no they dont die
37
Do cancer cells use the same regulator mechanisms of normal cells?
- no thats why they grow so quickly and uncontrolled
38
Are cancer cells genetically stable?
- no they are very unstable because they dont use normal regulatory mechanisms
- will produce new cells despite environment or DNA damage
39
What are the main classifications of cancer genes?
- genes that normally inhibit cellular proliferation
- genes that activate proliferation
- genes that participate in DNA repair
40
what are oncogenes?
- they are mutated forms of certain normal genes called pro-oncogenes
- oncogenes continue to divide
41
What are tumor suppressor genes?
- these are genes that slow down cell division, repair DNA mistakes, or tell cells when to die
- mutations in these genes leads to uncontrolled growth
42
What is an important distinction between oncogenes and tumor suppressor genes?
- oncogenes are turned on and continuously divide
| - tumor suppressor genes are turned off and can no longer inhibit growth
43
What was alfred knudsons original hypothesis?
- that a person needed to acquire two mutant copies of the Rb gene
44
How would somone acquire two copies of the mutant gene?
- one germline mutation inherited from one parent and then a somatic second mutation/event in the normal allele
45
What is the normal Rb protein function?
- to put a break on the cell cycle progession
46
What is inherited from parents with a mutant allele?
- a strong predisposition to develop a tumor
47
How does p16 function?
- binds to Cdk 4 and inhibits cyclin D from binding
48
When does p16 decide to bind to the cdk complex and stop cell proliferation?
- when there is stress in the cellular environment
49
What are factors that halt cell division and stimulate p53?
- hyperproliferative signals
- DNA damage
- Telomere shortening
- Hypoxia
50
What does p53 do when it is function correctly?
- cell cycle arrest
- senescence
- apoptosis
- all these things prevent further cell production
51
What does a mutation in the apc and Wnt b catenin pathway lead to?
- unligand activated signaling which leads to colon cancer
52
What is Wnt?
- wnt is a ligant that binds to a membrane receptor and induces cell signaling
53
Are virus genomes found in the form of DNA or RNA?
- both
54
Are virus genomes double stranded or single?
- both
55
Are virus genomes linear or circular?
- both
56
How many human cancers develop from virus genomes?
- 15%
57
What was the first viral oncogene identified?
- Avian Rous Sarcoma Virus (RSV)
58
What are the mutations usually found in when dealing with RNA viruses?
- oncogenes/protoncogenes
| - mitotic signal transduction pathways
59
What mutations do DNA tumor viruses normally have?
- mutations in tumor suppressor genes that affect cell cycle regulation
