cancer

Question 1

a tissue with abnormally high cell number (neoplasm)

Answer 1

tumor

Question 2

a malignant tumor that invades other tissues (metastasizes)

Answer 2

cancer

Question 3

describe the phases of cell cycle

Answer 3

1 -cell growth

s-DNA replication

2-rapid cell growth

m-separation of sister chromatids, cytokenesis

0-differentiated, senescent

Question 4

describe the important sites of quality control in the cell cycle (excluding cyclin)

Answer 4

1. restriction point
   
   1. G1
   2. arrests cyclce if no extracellular growth signal is present
2. DNA damage checkpoints
   
   1. G1,SG2
   2. arrests cyclce if DNA damage is detected, initates repair
3. DNA replication checkpoint
   
   1. S
   2. Arrests cycle if the replication fork is stalled, initiates repair
4. metaphase checkpoint
   
   1. arrests cycle until all chromosomes** correctly **attach to the mitotic spindle

Question 5

what are the signals that keep the cells in G0?

Answer 5

1. TGF-B
   
   1. induces differentiation of cells
2. contact inhibition
   
   1. cell-cell interactions through cadherin receptors
3. telomere shorteninig
   
   1. cell senescene to avoid loss of genetic material

Question 6

a cell is unable to repair the stalled replication fork what can be assumed about this cell?

Answer 6

The cell is stuck or DNA break in the S phase

• p53(TF) increases->
  
  • increases p21(CKI)->arrests cell cycle
  • GADD45(DNA repair enzyme)
• not repaired?
  
  • apoptosis initiated
    
    • IGF-BP3
      
      • inhibits apoptotic signal
    • Bax
      
      • activates apoptosis

cyclin DEAB

1. function
   
   1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
   2. activate specific cyclin dependent kinases
      
      1. phosphorylate target proteins
      2. promote cell cycle progression
2. regulation
   
   1. inducible
      
      1. cyclin
      2. Cycin dependent kinase inhibitor (CDKI)- binds to the cyclin-CDK complex
         
         1. additional other kinases* and *proteasomal degradative regulators are availabe
   2. constitutive
      
      1. cyclin dependent kinases (CDK)

Question 7

phosphorylate target proteins and promote cell cycle progression

Answer 7

cyclin DEAB

1. function
   
   1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
   2. activate specific cyclin dependent kinases
      
      1. phosphorylate target proteins
      2. promote cell cycle progression
2. regulation
   
   1. inducible
      
      1. cyclin
      2. Cycin dependent kinase inhibitor (CDKI)- binds to the cyclin-CDK complex
         
         1. D-CKI binds to D-CDK, inhibiting the phosphorylation of Rb. Rb can dephosphorylate or be destroyed and replaced->reassociating with E2F ->E2F-Rb, stops the progress from G1->S
         2. additional other kinases* and *proteasomal degradative regulators are availabe
   2. constitutive
      
      1. cyclin dependent kinases (CDK)
         
         1. growth factor stimulates Ras-Mek pathway activating D-CDK phosphorylates Rb, on the E2F-Rb complex. Rb releases E2F is a transcription factor that leads to integral genes for cell cycle progression to continue.

Question 8

describe the cyclins and their involvment in the cell cycle

Answer 8

1. function
   
   1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
   2. activate specific cyclin dependent kinases
      
      1. phosphorylate target proteins
      2. promote cell cycle progression

Question 9

Describe how the extracellular signals lead to the generation of cyclin proteins

Answer 9

growth factors are critical to cell growth and diversity

1. mitogens
   
   1. growth factors->receptor Y-kinase-> Ras->
2. mitogen acivated kinase cascades (MAPkinase cascades)
   
   1. cRaf->MEK->Erk1/2
3. other kinases and transcription factors
   
   1. p90rsk, cyclinD, etc
   2. growth

Question 10

Ras has decreased in stimulation, what is required to activate this pathway? What important MAPkinase cascade does Ras acivate?

Answer 10

growth factors are critical to cell growth and diversity

1. mitogens
   
   1. growth factors->receptor Y-kinase-> Ras->
2. mitogen acivated kinase cascades (MAPkinase cascades)
   
   1. cRaf->MEK->Erk1/2
3. other kinases and transcription factors
   
   1. p90rsk, cyclinD, etc
   2. growth

Question 11

Cells require cyclin to move through the restriction points and to progress to the different cell cycles. What do extracellular signals promote during this process?

Answer 11

growth factors are critical to cell growth and diversity

1. mitogens
   
   1. growth factors->receptor Y-kinase-> Ras->
2. mitogen acivated kinase cascades (MAPkinase cascades)
   
   1. cRaf->MEK->Erk1/2
3. other kinases and transcription factors
   
   1. p90rsk, cyclinD, etc
   2. growth

Question 12

describe the parameters that must be met in to commit to moving from the G1 phase in cell cycle replication. Think of the items that occur in G1, a cellmoving out of scensence

Answer 12

1. Adequate cell growth
   
   1. must preced DNA replication in S
2. Restriction point
   
   1. G1/S transition is controlled by the restriction point
3. sufficient cylcin D
   
   1. the transition point can only be passed if sufficient cyclin D is present
   2. cell growth will cause gradual increase in cycling D levels

debatable- decrease in the factors keepin the cell in G0=TGF-B

Question 13

the gate keeper of the restriction point

Answer 13

Retinoblastoma protein (Rb) is the gatekeeper of the restriction point

1. phosphorylation by D-CDK complexes inactivates Rb, and allows E2F trasncription factor to initiate cell cycle progression

Question 14

E2F-Rb never dissociates. What did not happen in

Answer 14

any of the following may have happend

1. Growth factor did not stimulate the cell
   
   1. any where during this pathway may have been hindered
2. Ras/Raf signal pathway did not induce synthesis of Cyclin D
3. CyclinD was not transcribed with high enough concentrations
4. CKI bound to E2F, may piggy back on #3

Retinoblastoma protein (Rb) is the gatekeeper of the restriction point

1. phosphorylation by D-CDK complexes inactivates Rb, and allows E2F trasncription factor to initiate cell cycle progression

Question 15

A DNA strand breaks or the suffers from a replication fork stall. What is the most likely of spots for this to happen and how is it handeled?

Answer 15

Ensure genomic integrity during interphase

1. if DNA is damaged, cell cycle is halted and repair is initiated
2. if repari is unsuccesful, apoptosis is initiated

certtain checkpoints are in place for detection of such events

1. DNA damage checkpoints
   
   1. G1,S,G2
   2. arrests cycle if DNA damage is detected, initate repairs
2. DNA replication checkpoint
   
   1. S
   2. arrests cycle if the replication fork is stalled, initiates repairs

Question 16

what is the main transducer leading to cell cycle arrest. Explain

Answer 16

Ensure genomic integrity during interphase

1. if DNA is damaged, cell cycle is halted and repair is initiated
2. if repari is unsuccesful, apoptosis is initiated

Question 17

what is the purpose of DNA damage/checkpoints?

Answer 17

Ensure genomic integrity during interphase

1. if DNA is damaged, cell cycle is halted and repair is initiated
   
   1. P53(TF)increases->
      
      1. p21
         
         1. is a CKI
      2. GADD45
         
         1. Repair DNA damage
2. if repair is unsuccesful, apoptosis is initiated
   
   1. IGF-BP3
      
      1. inhibits anti-apoptotic signals
   2. Bax
      
      1. activates apoptosis

Question 18

UV damage has caused DNA damage. when will the cell have a chance to become aware of this and how will it respond?

Answer 18

Ensure genomic integrity during interphase

1. stages of potential cognizants
   
   1. G1,S,G2
2. if DNA is damaged, cell cycle is halted and repair is initiated
   
   1. P53(TF)increases->
      
      1. p21
         
         1. is a CKI
      2. GADD45
         
         1. Repair DNA damage
3. if repair is unsuccesful, apoptosis is initiated
   
   1. IGF-BP3
      
      1. inhibits anti-apoptotic signals
   2. Bax
      
      1. activates apoptosis

Question 19

A cell undergoes replication fork stall. When will the cell have the oppotunity to gain aware of this?

Answer 19

Question 20

A cell undergoes DNA damage. When will the cell have the oppotunity to gain aware of this?

Answer 20

Question 21

describe the proteins that are activated and how leading to cell death?

Answer 21

caspases are cysteine proteases

• proenzymes acivated by protelytic cleavage
  
  • initators (8,9,10)
    
    • activated directly by the death cell receptor and mitochondrial pathway
  • execution(3,6,7)
    
    • activated by initiator caspases
    • cleave many different proteins in the cell
      
      • actin
      • proteins of the nuclear envelope
      • DNA repair enzymes (GADD45)
      • inhibitors of caspase dependent endonucleases

1. normal physiological process
   
   1. embryogenesis
   2. maintenance of proper cell number
   3. removal of injured cells
2. inition pahways
   
   1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      
      1. death receptor
      2. mitochondrial
3. outcome
   
   1. caspase cascade leads to
      
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

Question 22

GADD45 is unable to complete its job, what is the cell going to do next?

Answer 22

He is going to get chopped up by the execution caspases (3,6,7)

1. normal physiological process
   
   1. embryogenesis
   2. maintenance of proper cell number
   3. removal of injured cells
2. inition pahways
   
   1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      
      1. death receptor
      2. mitochondrial
3. outcome
   
   1. caspase cascade leads to
      
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

Question 23

what is the purpose of apoptosis

Answer 23

1. normal physiological process
   
   1. embryogenesis
   2. maintenance of proper cell number
   3. removal of injured cells
2. inition pahways
   
   1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      
      1. death receptor
      2. mitochondrial
3. outcome
   
   1. caspase cascade leads to
      
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

Question 24

A CT-cell tells a cancerous cell to die. What is the pathway?

Answer 24

death receptor of apoptosis

1. initiator caspases are activated
   
   1. 8,9,10
2. Execution caspase are activate
   
   1. 3,6,7
      
      1. activate Bid
         
         1. stimulates the mitochondrial pathway
      2. chromatin condensation
      3. DNA fragmentation
      4. cell shrinkage

Question 25

Bax is generated but relies on what else to be operational?

Answer 25

1. DNA damage repair was unsuccesful
   
   1. IGF-BP3
      
      1. anti-apoptotic signal
   2. Bax
      
      1. CDKI
2. Bax will supress the CDK and there will be a decline in cyclin. Stopping the cell growth
3. death signal is sent to the mitochondria and the causes the release of cyt-c
4. cyt-c binds to tapoptotic pretease activating factor-1 (Apaf-1)
5. Apaf-1 -cyt-C complex activates the initiation caspase-9
6. Caspase 9 activates exectution caspases - 3,6,7
   
   1. Bid activation
      
      1. Bid binds to Bax and BidBax complex generates a channel in the mitochondrial membrane
   2. chromatin condensation
   3. DNA fragmentation
   4. cell shrinkage

Question 26

The constant expression of IGF-BP3 and Bax leads has what outcome?

Answer 26

1. DNA damage repair was unsuccesful
   
   1. IGF-BP3
      
      1. anti-apoptotic signal
   2. Bax
      
      1. CDKI
2. Bax will supress the CDK and there will be a decline in cyclin. Stopping the cell growth
3. death signal is sent to the mitochondria and the causes the release of cyt-c
4. cyt-c binds to tapoptotic pretease activating factor-1 (Apaf-1)
5. Apaf-1 -cyt-C complex activates the initiation caspase-9
6. Caspase 9 activates exectution caspases - 3,6,7
   
   1. Bid activation
      
      1. Bid binds to Bax and BidBax complex generates a channel in the mitochondrial membrane
   2. chromatin condensation
   3. DNA fragmentation
   4. cell shrinkage

Question 27

The body begins to decrease the growth factor att certain ages, what happens to some cells as this decline is complete?

Answer 27

apoptosis depends on the ratio of pro- anti-apoptotic molecules. A decrease in the growth factors leads to and increase in Bid. Bid must compete with Bcl-2 to find Bax.

1. pro-apoptotic
   
   1. Bax
      
      1. form channels in the outer mitochondrial membran to release Cyt-C, butt function depends on binding of Bh3-only members (Bid)
   2. Bid
      
      1. regulare tthe activity of the channel forming pro-apoptotic factors
2. anti-apoptotic
   
   1. Bcl-2
      
      1. sequesters BH3-only members away from the channel forming pro-apoptotic factos
      2. can bind and inativate Apaf-1

Question 28

list the important pro-/anti- apoptotic factors and their operation

Answer 28

1. pro-apoptotic
   
   1. Bax
      
      1. form channels in the outer mitochondrial membran to release Cyt-C, butt function depends on binding of Bh3-only members (Bid)
   2. Bid
      
      1. regulare tthe activity of the channel forming pro-apoptotic factors
2. anti-apoptotic
   
   1. Bcl-2
      
      1. sequesters BH3-only members away from the channel forming pro-apoptotic factos
      2. can bind and inativate Apaf-1

Question 29

Smoking increases exposure of what chemicals? how does this affect the cell?

Answer 29

carcinogens and radiation cause DNA modification

1. smoking increases polycyclic hydrocarbon exposure, which turns in to epoxides and alters DNA. An alteration in the DNA may lead to lung cancer

look at the sequential order benign->malignant

Question 30

describe the formation of cancer

Answer 30

look at the sequential order benign->malignant

Question 31

define the following for proto-oncogenes and tumor-supressors

1. normal function in cell groth and proliferation
2. normal function in cell death
3. normal function in cell number regulation
4. genetic changes in tumor formation
5. alleles mutated in tumors

Answer 31

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 32

define the normal function of protoncogens and tumor suppresors in cell growth and proliferation

Answer 32

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 33

describe the normal function of proto oncogens and tumor suppressors in cell death

Answer 33

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 34

describe the function of proto oncogenes and tumor suppressors in cell number regulation

Answer 34

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 35

describe the genetic changes in tumors formation with respect to proto oncogenes and tumor suppressors

Answer 35

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 36

Describe the alleles mutated for proto oncogens and tumor supressors with respect to tumors

Answer 36

1. normal function in cell groth and proliferation
   
   1. PO
      
      1. induce cell growth or proliferation
   2. TS
      
      1. inhibit cell growth or proliferation
2. normal function in cell death
   
   1. PO
      
      1. inhibit cell death anti-apoptotic
   2. TS
      
      1. induce cell death (pro)-apoptotic
3. normal function in cell number regulation
   
   1. PO
      
      1. increase cell number
   2. TS
      
      1. decrease cell number
4. genetic changes in tumor formation
   
   1. PO
      
      1. gain of function mutations (OVERACTIVATION)
   2. TS
      
      1. loss of function mutations (INACTIVATION)
5. alleles mutated in tumors
   
   1. PO
      
      1. generally one allele is overactivates
   2. TS
      
      1. both alleles must be inactivated

Question 37

overactivated proto-oncogens

Answer 37

overactivated proto-oncogenes are called oncogenes

Question 38

list the important proto-oncogen examples for the following

1. receptors
2. signal transduction molecules
3. transcription factors
4. epigenetic modifiers
5. telomerase
6. anti-apoptotic factors
7. cell-cycle inducers

Answer 38

1. receptors
   
   1. EGF receptor-breast cancer
2. signal transduction molecules
   
   1. Ras, Abl
3. transcription factors
   
   1. Myc
4. epigenetic modifiers
   
   1. histone acyltransferase-increase in activity
5. telomerase
   
   1. telomerase- overactivity
6. anti-apoptotic factors
   
   1. Bcl-2
7. cell-cycle inducers
   
   1. cyclins

Question 39

list examples of proto oncogen receptors and signal transduction factors

Answer 39

1. receptors
   
   1. EGF receptor-breast cancer
2. signal transduction molecules
   
   1. Ras, Abl
3. transcription factors
   
   1. Myc
4. epigenetic modifiers
   
   1. histone acyltransferase-increase in activity
5. telomerase
   
   1. telomerase- overactivity
6. anti-apoptotic factors
   
   1. Bcl-2
7. cell-cycle inducers
   
   1. cyclins

Question 40

list examples of proto oncogen transcritption factos and epigenetic modifiers

Answer 40

1. receptors
   
   1. EGF receptor-breast cancer
2. signal transduction molecules
   
   1. Ras, Abl
3. transcription factors
   
   1. Myc
4. epigenetic modifiers
   
   1. histone acyltransferase-increase in activity
5. telomerase
   
   1. telomerase- overactivity
6. anti-apoptotic factors
   
   1. Bcl-2
7. cell-cycle inducers
   
   1. cyclins

Question 41

list examples of proto oncogen telomerase, anti-apoptotic factos, and cell-cycle inducers

Answer 41

1. receptors
   
   1. EGF receptor-breast cancer
2. signal transduction molecules
   
   1. Ras, Abl
3. transcription factors
   
   1. Myc
4. epigenetic modifiers
   
   1. histone acyltransferase-increase in activity
5. telomerase
   
   1. telomerase- overactivity
6. anti-apoptotic factors
   
   1. Bcl-2
7. cell-cycle inducers
   
   1. cyclins

Question 42

list conversion three ways to convert a proto oncogene into an oncogene(general)

Answer 42

1. radiation or chemical carcinogen
   
   1. mutation in coding region causes production of hyper active protein
   2. mutation in promoter causes excessive expression
2. gene rearrangement
   
   1. proto-oncogene is now under control of strong promtoers or enhance
   2. prot-oncogene or a portion of it is fused with another gene
      
      1. fusion protein is either overproduced or hyperactive
3. gene amplification
   
   1. expression of multiple copies of the prot-oncogene

Question 43

list the possible effects and locations for radiation or chemical carcinogens affects on proto-oncogens

Answer 43

1. radiation or chemical carcinogen
   
   1. mutation in coding region causes production of hyper active protein
   2. mutation in promoter causes excessive expression
2. gene rearrangement
   
   1. proto-oncogene is now under control of strong promtoers or enhance
   2. prot-oncogene or a portion of it is fused with another gene
      
      1. fusion protein is either overproduced or hyperactive
3. gene amplification
   
   1. expression of multiple copies of the prot-oncogene

Question 44

list the two possible ways for genetic rearrangment to generat a oncogene from a proto-oncogene

Answer 44

1. radiation or chemical carcinogen
   
   1. mutation in coding region causes production of hyper active protein
   2. mutation in promoter causes excessive expression
2. gene rearrangement
   
   1. proto-oncogene is now under control of strong promtoers or enhance
   2. prot-oncogene or a portion of it is fused with another gene
      
      1. fusion protein is either overproduced or hyperactive
3. gene amplification
   
   1. expression of multiple copies of the prot-oncogene

Question 45

What can lead to the expression of multiple copies of the proto-oncogene?

Answer 45

1. radiation or chemical carcinogen
   
   1. mutation in coding region causes production of hyper active protein
   2. mutation in promoter causes excessive expression
2. gene rearrangement
   
   1. proto-oncogene is now under control of strong promtoers or enhance
   2. prot-oncogene or a portion of it is fused with another gene
      
      1. fusion protein is either overproduced or hyperactive
3. gene amplification
   
   1. expression of multiple copies of the prot-oncogene

Question 46

List the following for CML

1. chromosome translocation
2. the overactivates proto-oncogene

Answer 46

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 47

List the following for burkitt lympohoma

1. chromosome translocation
2. the overactivates proto-oncogene

Answer 47

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 48

List the following for follicular lymphoma

1. chromosome translocation
2. the overactivates proto-oncogene

Answer 48

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 49

List the following for mantle lymphoma

1. chromosome translocation
2. the overactivates proto-oncogene

Answer 49

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 50

what are the diseases

1. t(9;22) with an increase in this gene BCR-ABL
2. t(8;14), t(8;22), t(2;8) with an increase in this gene MYC

Answer 50

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 51

what are the diseases ?

1. t(14;18) with an increase in BCL-2
2. t(11;14) with an increase in cyclinD

Answer 51

1. chronic mylogenous leukemia (CML)
   
   1. t(9;22)
   2. BCR-ABL
2. Burkitt lymphoma
   
   1. t(8;14), t(8;22), t(2;8)
   2. MYC
3. follicular lymphoma
   
   1. t(14;18)
   2. BCL-2
4. mantle cell lymphoma
   
   1. t(11;14)
   2. cyclinD

Question 52

How can the asminstration of Geevac assist an individual with altered philidelphia c’some t(9;22)?

Answer 52

1. ABL proto oncogene (tyrosine kinase) is tranlocate from chromosome 9 to chromosome 22, and it is joined to the BCR gene
2. BCR-ABL chimeric protein
   
   1. increased Y-kinase activity
3. philidelphia chromosome
   
   1. altered chromosome 22
4. cause
   
   1. escessive proliferation of myeloid precursosrs in bone marrow, leading to elevated levels of granulocytes in the blood
5. managed
   
   1. tyrosine inhibitors
      
      1. Gleevac

Question 53

explain the type of gene conversion associated with CML.

Answer 53

1. ABL proto oncogene (tyrosine kinase) is tranlocate from chromosome 9 to chromosome 22, and it is joined to the BCR gene
2. BCR-ABL chimeric protein
   
   1. increased Y-kinase activity
3. philidelphia chromosome
   
   1. altered chromosome 22
4. cause
   
   1. escessive proliferation of myeloid precursosrs in bone marrow, leading to elevated levels of granulocytes in the blood
5. managed
   
   1. tyrosine inhibitors
      
      1. Gleevac

Question 54

This mutation causes excessive proliferation of myeloid precursors in bone marrow- leading to elevated levels of granulocytes

How is this disease managed?

Answer 54

1. ABL proto oncogene (tyrosine kinase) is tranlocate from chromosome 9 to chromosome 22, and it is joined to the BCR gene
2. BCR-ABL chimeric protein
   
   1. increased Y-kinase activity
3. philidelphia chromosome
   
   1. altered chromosome 22
4. cause
   
   1. excessive proliferation of myeloid precursosrs in bone marrow, leading to elevated levels of granulocytes in the blood
5. managed
   
   1. tyrosine inhibitors
      
      1. Gleevac

Question 55

describe the condition associated with t(9;22)

Answer 55

1. ABL proto oncogene (tyrosine kinase) is tranlocate from chromosome 9 to chromosome 22, and it is joined to the BCR gene
2. BCR-ABL chimeric protein
   
   1. increased Y-kinase activity
3. philidelphia chromosome
   
   1. altered chromosome 22
4. cause
   
   1. escessive proliferation of myeloid precursosrs in bone marrow, leading to elevated levels of granulocytes in the blood
5. managed
   
   1. tyrosine inhibitors
      
      1. Gleevac

Question 56

Describe the following for t(8;14)

1. type of gene conversion?
2. what is the promtor that controls the gene? explain

Answer 56

burkitts lymphoma

1. myc proto-oncogene is tranlocated from chromosome 9->14 (gene rarrangement)
2. MYC is now controlled by the promoter region of the IgHeavy chain genes
   
   1. smaller % of cases are caused by MYC translocation behind the promter region of Iglight chains
3. MYC protein is a transcription factor and will be overexpressed in B-cells, promoting cell growth and proliferation
4. patient features
   
   1. B-cell tumors in jaw

Question 57

A patient appears with tumors that cause a deformation of the jaw. Samples come back as B-cell tumors. what is the disease and what type of mutation occured/where?

Answer 57

1. myc proto-oncogene is tranlocated from chromosome 9->14
2. MYC is now controlled by the promoter region of the IgHeavy chain genes
   
   1. smaller % of cases are caused by MYC translocation behind the promter region of Iglight chains
3. MYC protein is a transcription factor and will be overexpressed in B-cells, promoting cell growth and proliferation
4. patient features
   
   1. B-cell tumors in jaw

Question 58

A disease is associated with a proto-oncogene translocating next to a heavy chain immunoglobulin promter and being OVER expressed. The anti-apoptotic factor is NOT affected and the cyclin D is at normal levels.

Answer 58

Burkitt lymphoma

1. myc proto-oncogene is tranlocated from chromosome 8->14
2. MYC is now controlled by the promoter region of the IgHeavy chain genes
   
   1. smaller % of cases are caused by MYC translocation behind the promter region of Iglight chains
3. MYC protein is a transcription factor and will be overexpressed in B-cells, promoting cell growth and proliferation
4. patient features
   
   1. B-cell tumors in jaw

Question 59

Patients blood work shows an incredibly high B-cell count and the genes show the following:t(18;14)

what is the disease and what type of conversion took place

Answer 59

1. translocation moves Bcl-2 proto oncogene from chromosome 18 to chromosome 14 and places it under the promoter control of immunoglobulin heavy chain genes, so Bcl-2 will be over expressed in B-cells
2. BCL-2 protein is an anti-apoptotic factor
3. elevated BCL-2 protein will prevent death of B cells which leads to massive expansion of B-cell populations

Question 60

BCL-2 protein is over expressed in a patients B-cell population.

1. describe the disease
2. factor affected

Answer 60

1. translocation moves Bcl-2 proto oncogene from chromosome 18 to chromosome 14 and places it under the promoter control of immunoglobulin heavy chain genes, so Bcl-2 will be over expressed in B-cells
2. BCL-2 protein is an anti-apoptotic factor
3. elevated BCL-2 protein will prevent death of B cells which leads to massive expansion of B-cell populations

Question 61

increase in what protein is associated with t(11;14)?

1. disease
2. protein

Answer 61

mantle cell lymphoma

1. translocation moves cyclin D1 proto-oncogene from chromosome 11->14 and places it under the promoter control of Igheavy chain genes and will be overexpressed in B cells
2. cyclin D1 drives the G1phase in the cell cycle
3. high cyclin D1 in B cells will cause increased proliferation, which leads to B-cell lymphoma

Question 62

Mantle cell lymphoma is a disease associated with what type of conversion? explain

Answer 62

1. translocation moves cyclin D1 proto-oncogene from chromosome 11->14 and places it under the promoter control of Igheavy chain genes and will be overexpressed in B cells
2. cyclin D1 drives the G1phase in the cell cycle
3. high cyclin D1 in B cells will cause increased proliferation, which leads to B-cell lymphoma

Question 63

High cyclin D is noted in a patient sample of B cells taken from the blood. Explain the disease and known conversion.

Answer 63

1. translocation moves cyclin D1 proto-oncogene from chromosome 11->14 and places it under the promoter control of Igheavy chain genes and will be overexpressed in B cells
2. cyclin D1 drives the G1phase in the cell cycle
3. high cyclin D1 in B cells will cause increased proliferation, which leads to B-cell lymphoma

Question 64

a patient presents with the following

1. upregulated genes from c’some 14
2. Ig heavy chain promoter
3. increased B cell proliferation

what diseases could it be and what could you look at to dissociate them?

Answer 64

Question 65

A patient presents with a lump on their cervix. describe the following

1. disease that should be screened
2. what this infectious agent acts on?
3. explain the process involved
   
   1. two proteins are affected

Answer 65

1. paipilloma virus
   
   1. proetins of teh virus inactivate tumor suppresors Rb and p53
   2. causes cervical cancer
2. HTLV-1(human T-cell lymphotropic virus 1)
   
   1. the tax protein of the virus is a coactivator of proto-oncogenes
   2. causes T-cell leukemia
3. HIV(human immunodefency virus)
   
   1. the Tat transcription factor of the virus activates the synthesis of cytokines, which promotes T-cell proliferation
   2. causes
      
      1. non-hodgkins lymphoma

Question 66

This virus causes T-cell leukemia

Answer 66

1. paipilloma virus
   
   1. proetins of teh virus inactivate tumor suppresors Rb and p53
   2. causes cervical cancer
2. HTLV-1(human T-cell lymphotropic virus 1)
   
   1. the tax protein of the virus is a coactivator of proto-oncogenes
   2. causes T-cell leukemia
3. HIV(human immunodefency virus)
   
   1. the Tat transcription factor of the virus activates the synthesis of cytokines, which promotes T-cell proliferation
   2. causes
      
      1. non-hodgkins lymphoma

Question 67

a patient with HIV has a higher risk of developing what disease with T-cells?

Answer 67

1. paipilloma virus
   
   1. proetins of teh virus inactivate tumor suppresors Rb and p53
   2. causes cervical cancer
2. HTLV-1(human T-cell lymphotropic virus 1)
   
   1. the tax protein of the virus is a coactivator of proto-oncogenes
   2. causes T-cell leukemia
3. HIV(human immunodefency virus)
   
   1. the Tat transcription factor of the virus activates the synthesis of cytokines, which promotes T-cell proliferation
   2. causes
      
      1. non-hodgkins lymphoma

Question 68

list the associated types of tumor suppressors

1. receptors
2. signal transduction molecules
3. transcription factos
4. epigenetic modifiers
5. pro-apoptotic factors
6. cell-cycle regulators
7. DNA repair molecules

Answer 68

1. receptors
   
   1. TGFB receptor
2. signal transduction molecules
   
   1. NF-1
3. transcription factos
   
   1. p53
4. epigenetic modifiers
   
   1. histone acetyltransferase- silenced
5. pro-apoptotic factors
   
   1. death receptors-cell cannot dies via WBC
6. cell-cycle regulators
   
   1. Rb
7. DNA repair molecules
   
   1. BRCA1-cancer formation is dependent on mutation

Question 69

list exaples of receptor and signal transduction tumor suppressors

Answer 69

1. receptors
   
   1. TGFB receptor
2. signal transduction molecules
   
   1. NF-1
3. transcription factos
   
   1. p53
4. epigenetic modifiers
   
   1. histone acetyltransferase- silenced
5. pro-apoptotic factors
   
   1. death receptors-cell cannot dies via WBC
6. cell-cycle regulators
   
   1. Rb
7. DNA repair molecules
   
   1. BRCA1-cancer formation is dependent on mutation

Question 70

list an important transcription factor, epigenetic modifier and pro-apoptotic factor tumor suppresor

Answer 70

1. receptors
   
   1. TGFB receptor
2. signal transduction molecules
   
   1. NF-1
3. transcription factos
   
   1. p53
4. epigenetic modifiers
   
   1. histone acetyltransferase- silenced
5. pro-apoptotic factors
   
   1. death receptors-cell cannot dies via WBC
6. cell-cycle regulators
   
   1. Rb
7. DNA repair molecules
   
   1. BRCA1-cancer formation is dependent on mutation

Question 71

list cellcycle regulator and DNA repair molecule tumor suppressors

Answer 71

1. receptors
   
   1. TGFB receptor
2. signal transduction molecules
   
   1. NF-1
3. transcription factos
   
   1. p53
4. epigenetic modifiers
   
   1. histone acetyltransferase- silenced
5. pro-apoptotic factors
   
   1. death receptors-cell cannot dies via WBC
6. cell-cycle regulators
   
   1. Rb
7. DNA repair molecules
   
   1. BRCA1-cancer formation is dependent on mutation

Question 72

describe the two hit theory and its inactivation of tumor supressor genes and the sources

Answer 72

inactivation of tumor suppressor genes-two hit theory

1. germline disease
   
   1. mostly autosomal dominant- seen in every generation
2. sporadic
   
   1. majority of tumors
   2. 95% in elderly

sources

1. loss of heterozygosity
   
   1. loss of the entire normal gene
      
      1. deletion
      2. mitotic, non-disjunction
      3. abnormal mitotic c’some recombination
2. loss of function
3. epigenetic silencing of normal allele

Question 73

What type of change is associated with retinoblastoma? explain

Answer 73

1. Rb is a tumor suppressor that regulates the G1/S cell cycle progression by sequestering the E2F transcription factor
2. mutations in Rb lead to tumor in the retina (retinoblastoma)
3. the cancer has both heritable and sporadic form.

Question 74

a child presents with a white reflection of the retina. explain the two forms

Answer 74

1. Rb is a tumor suppressor that regulates the G1/S cell cycle progression by sequestering the E2F transcription factor
2. mutations in Rb lead to tumor in the retina (retinoblastoma)
3. the cancer has both heritable and sporadic form.

Question 75

80 year patient presents with a tumor wich has a loss of function mutation in the p53. What is this type of cancer and what are the normal/impaired functions of the protein?

Answer 75

1. DNA damage increases the level and activation of p53 protein
2. p53 protein is a transcritption factor that induces the production of proteins that
   
   1. p21
      
      1. CKI, arresting cell cylce
   2. GADD45
      
      1. DNA repair enzymes
   3. unsuccesful- apoptosis
      
      1. IGF-BP3 and Bax
3. consequence
   
   1. defective p53 associated with almost all sporadic cancers

Question 76

A cell line is unable to stop the cell cycle after detecting damage to the DNA. Where could the mutation be? explain the mutation and the normal/impaired functions associated

Answer 76

1. DNA damage increases the level and activation of p53 protein
2. p53 protein is a transcritption factor that induces the production of proteins that
   
   1. p21
      
      1. CKI, arresting cell cylce
   2. GADD45
      
      1. DNA repair enzymes
   3. unsuccesful- apoptosis
      
      1. IGF-BP3 and Bax
3. consequence
   
   1. defective p53 associated with almost all sporadic cancers

Question 77

a patient speaks with a physician about the multiple types of cancer seen in his family: breast, sarcoma and other malignant neoplasms. What could this be mutation in?

Answer 77

1. Li-Fraumeni syndrome
   
   1. hereditary cancer caused by p53 mutations
   2. multiple types of cancers in families

Question 78

hereditary cancer caused by p53 mutations

Answer 78

1. Li-Fraumeni syndrome
   
   1. hereditary cancer caused by p53 mutations
   2. multiple types of cancers in families

Question 79

patient sample presents with cafe au lait spots and freckles just under the armpits. What could this be associated with? Where is the mutation?

Answer 79

neruofibromatosis type1

1. neurofibromin-1 (NF-1)
   
   1. regulates the activity of RAS (proto-oncogene) in the Y-kinase receptor pathway) in peripheral nerve sheets
   2. RAS is active as long as it is bound to GTP
   3. NF-1 binds to RAS and activates the GTPase domain of RAS
   4. GTP is hydrolyzed to GDP, and RAS becomes inactive
   5. Cause
      
      1. loss of function mutation in NF-1 lead to overactivation of RAS in peripheral nerve sheets and neurofobromatosis type1

Question 80

A mutation here leads to an inactivation of RAS. Is this a proto-oncogene or a tumor supressor gene? What is RAS?

Answer 80

1. neurofibromin-1 (NF-1)- tumor supressor (inactivate a proto-oncogene)
   
   1. regulates the activity of RAS (proto-oncogene) in the Y-kinase receptor pathway) in peripheral nerve sheets
   2. RAS is active as long as it is bound to GTP
   3. NF-1 binds to RAS and activates the GTPase domain of RAS
   4. GTP is hydrolyzed to GDP, and RAS becomes inactive
   5. loss of function mutation in NF-1 lead to overactivation of RAS in peripheral nerve sheets and neurofobromatosis type1

Question 81

loss of function mutation in NF-1 leads to what disease?

Answer 81

1. neurofibromin-1 (NF-1)
   
   1. regulates the activity of RAS (proto-oncogene) in the Y-kinase receptor pathway) in peripheral nerve sheets
   2. RAS is active as long as it is bound to GTP
   3. NF-1 binds to RAS and activates the GTPase domain of RAS
   4. GTP is hydrolyzed to GDP, and RAS becomes inactive
   5. loss of function mutation in NF-1 lead to overactivation of RAS in peripheral nerve sheets and neurofobromatosis type1

Question 82

Cell-cell interaction includes two important attachments. Explain the relationship, are they and are they PO or TS?

Answer 82

1. healthy
   
   1. cell-cell contact arrests the cell cycle in the G0/G1 stage
   2. cell-cell contact is mediated by E-cadherin(tumor supressor)
      
      1. binds to a potent proto-oncogene b-catenin
2. disease- adenomatous polyposis coli (APC)
   
   1. ​b-catenin, PO, induces expression of MYC
      
      1. MYC-transcriptional co-activator that promotes cell cycle
   2. APC is a tumor suppressor that targets b-catenin for degradation
   3. APC mutations are associated with
      
      1. ​familial adenomatous polyposis (colon cancer)

Question 83

E-cadherin binds to other cells and b-catenin. what happens if the b-catenin dissociates? normal/disease?

Answer 83

1. healthy
   
   1. cell-cell contact arrests the cell cycle in the G0/G1 stage
   2. cell-cell contact is mediated by E-cadherin(tumor supressor)
      
      1. binds to a potent proto-oncogene b-catenin
2. disease- adenomatous polyposis coli (APC)
   
   1. ​b-catenin, PO, induces expression of MYC
      
      1. MYC-transcriptional co-activator that promotes cell cycle
   2. APC is a tumor suppressor that targets b-catenin for degradation
   3. APC mutations are associated with
      
      1. ​familial adenomatous polyposis (colon cancer)

Question 84

mutation in APC causes what? how? is it a PO or TS?

Answer 84

1. healthy
   
   1. cell-cell contact arrests the cell cycle in the G0/G1 stage
   2. cell-cell contact is mediated by E-cadherin(tumor supressor)
      
      1. binds to a potent proto-oncogene b-catenin
2. disease- adenomatous polyposis coli (APC)
   
   1. ​b-catenin, PO, induces expression of MYC
      
      1. MYC-transcriptional co-activator that promotes cell cycle
   2. APC is a tumor suppressor that targets b-catenin for degradation
   3. APC mutations are associated with
      
      1. ​familial adenomatous polyposis (colon cancer)

Question 85

mutation in what tumor suppresor gene can lead to accumulation of mutations?

Answer 85

DNA repair genes as tumor suppresors

1. repair is an important component of the cell cycle. If not impolemented correctly, result in apoptosis or mutation accumulation
2. BRCA1 and 2
   
   1. hereditary breast and ovarian cancer
   2. autosomal dominant

Question 86

inherted in an autossomal dominant pattern. Can lead to breast and ovarian cancer.

Answer 86

DNA repair genes as tumor suppresors

1. repair is an important component of the cell cycle. If not impolemented correctly, result in apoptosis or mutation accumulation
2. BRCA1 and 2
   
   1. hereditary breast and ovarian cancer
   2. autosomal dominant

Question 87

BRCA1 and BRCA2 are well known PO or TS?

explain how mutations here are associated with cancer development.

Answer 87

DNA repair genes as tumor suppresors

1. repair is an important component of the cell cycle. If not impolemented correctly, result in apoptosis or mutation accumulation
2. BRCA1 and 2
   
   1. hereditary breast and ovarian cancer
   2. autosomal dominant

Question 88

this is followed by multiple mutations in proto-oncogens and/or tumor suppressor genes. explain useing APC as an example

Answer 88

tumor to cancer transformation

1. formation of cancers start with a driver mutation followed by multiple muations in proto-oncogens and/or tumor suppresor genes
2. example is the formation of sporadic colon cancer

adenomas: benign tumors of glandular/epithelial origin

Question 89

APC mutation is associated with the term “driver muation” explain.

Answer 89

tumor to cancer transformation

1. formation of cancers start with a driver mutation followed by multiple muations in proto-oncogens and/or tumor suppresor genes
2. example is the formation of sporadic colon cancer

Question 90

adenomase: benign tumors of glandular/epithelial origin

Answer 90

tumor to cancer transformation

1. formation of cancers start with a driver mutation followed by multiple muations in proto-oncogens and/or tumor suppresor genes
2. example is the formation of sporadic colon cancer