Genetic Origins of Cancer

Question 1

oncogenes are..

Answer 1

genes that have acquired the ability to induce normal characteristics of cancer cells

Question 2

A normal oncogene is called…

Answer 2

a proto-oncogene

Question 3

2 characteristics of tumor suppressor genes

Answer 3

1. cellular brakes
2. cannot arrest proliferation when mutated

Question 4

list the 6 hallmarks of cancer

Answer 4

1. self-sufficiency in growth signals
2. insensitivity to antigrowth signals
3. evasion of apoptosis
4. limitless replicative potential
5. sustained angiogenesis
6. tissue invasion and metastasis

Question 5

the concept of endogenous retroviruses were modeled in

Answer 5

the 1970s

Question 6

the concept of endogenous retroviruses attempted to explain

Answer 6

how tumor viruses might initiate numerous cancers that showed no symptoms of viral infections

Question 7

Have endogenous proviruses been acquired in germs lines of both humans and mammals?

Answer 7

no, just in mammals

Question 8

name a virus that has the potential to cause cancer

Answer 8

HPV virus

Question 9

what is the mechanism of viruses that cause cancer?

Answer 9

insertion of a viral oncogene or induction of tissue damage

Question 10

explain the translocation of the Philadelphia chromosome

Answer 10

exchange between ABL gene in chromosome 9 w/ the BCR gene in chromosome 22

Question 11

which chromosome is known as the Philadelphia chromosome?

Answer 11

shortened chromosome 22

Question 12

the gene product of the philadelphia chromosome leads to the development of what cancers

Answer 12

leukemias

Question 13

list 3 other types of DNA arrangements

Answer 13

1. deletion/ insertion
2. transpositions
3. inversion

Question 14

how do ras mutants result in an active protein

Answer 14

by not being able to carry out GTP hydrolysis

Question 15

what does MAPK stand for

Answer 15

mitogen-activated protein kinase

Question 16

EGF signal transduction is characterized by what 4 characteristics

Answer 16

• GF binding
• receptor dimerization, cross phosphorylation
• activation of internal kinase cascade
• transcription/ gene expression

Question 17

explain how a truncated receptor leads to deregulated growth factor signaling

Answer 17

emits signals even in the absence of ligand binding

Question 18

what growth factor is suspected in autophosphorylation

Answer 18

EGF

Question 19

what GF is dimerized by a heparin link

Answer 19

FGF2

Question 20

what single molecule simultaneously contacts 2 receptor monomers causing dimerization?

Answer 20

EPO (erythropoietin)

Question 21

what ligand molecules may bind 2 monomeric receptors exposing 2 activation sites?

Answer 21

TGFa

Question 22

what is the effect of GF on platelet cells

Answer 22

when activated the secretory vessels containing GF fuse with PM and release mitogens

Question 23

TRK oncogene is a…

Answer 23

chromosomal inversion on the same chromosome (fusion gene)

Question 24

fusion gene of the TRK oncogene causes the

Answer 24

receptor region to remain dimerized and its kinase becomes constitutively activated

Question 25

STAT stands for

Answer 25

signal transduction and activation of transcription

Question 26

in what pathway of cell proliferation is the kinase not built into the receptor?

Answer 26

the Jak-STAT pathway

Question 27

list the 5 different types of abnormalities that can result in proto-oncogenes

Answer 27

1. point mutation 2. gene amplification 3. chromosomal translocation 4. local DNA arrangements 5. insertional mutagenesis (viral DNA)

Question 28

ras oncogenes differ from their proto-oncogenes by point mutations resulting in...

Answer 28

single substitutions at critical positions where Gly is changed for Val

Question 29

what act as brakes that slow down cell cycle progression?

Answer 29

proteins encoded by tumor suppressor genes

Question 30

what is known as the prototype of a tumor suppressor gene?

Answer 30

Rb

Question 31

what is the target of tumor suppressor genes that is often mutated in a number of different human tumors?

Answer 31

cyclin D/ Cdk4,6

Question 32

b/c a single oncogene is requires to produce cancer oncogenes are characterized as

Answer 32

exhibiting dominant behavior

Question 33

with tumor suppressor genes _____ copies must become ________ becoming _____ and leading to _____.

Answer 33

both non-functional recessive cancer

Question 34

when active Rb binds to E2F transcription factor it prevents:

Answer 34

-transcription of genes for DNA replication - passage from G1 into S phase

Question 35

a phosphorylated Rb can NOT bind to E2F causing...

Answer 35

- E2F to activate gene transcription (onto S phase) - dephosphorylated Rb returns to inhibit E2F

Question 36

what type of experiments demonstrate that cancer is of a recessive phenotype

Answer 36

cell fusion experiments

Question 37

explain a cell fusion experiment

Answer 37

a cancer and normal cell are fused the fused cell divides and the new nuclei contains chromosomes from original cells. results in a hybrid cell w/ normal growth. hybrid cell divides and chromosomes are lost resulting in a cancer cell w/ uncontrolled growth

Question 38

in a cell fusion experiment reversion of the cancer phenotype is due to..

Answer 38

the loss of tumor suppressor genes

Question 39

what are the 2 different types of inheritance patterns of mutation genes?

Answer 39

recessive cancer-risk syndrome dominant cancer-risk syndrome

Question 40

in recessive cancer-risk syndrome...

Answer 40

2 copies of tumor suppressor genes must be inherited to create a high risk of developing cancer

Question 41

in dominant cancer-risk syndrome

Answer 41

a single defective tumor suppressor gene is sufficient to cause high risk of getting cancer, but a second gene is required before cancer can actually arise

Question 42

what allows for functional tumor suppression?

Answer 42

heterozygosity

Question 43

what is loss of heterozygosity?

Answer 43

when a normal chromosome becomes disrupted bc of the mutated chromosome

Question 44

list the 3 types of loss of heterozygosity

Answer 44

1. mitotic nondisjunction 2. mitotic recombination 3. gene conversion

Question 45

explain mitotic nondisjunction

Answer 45

duplicate copies of the normal chromosome fail to divide at the time of mitosis causing both copies to go into one cell and the other cell is left with the mutated chromosome

Question 46

explain mitotic recombination

Answer 46

2 homologous chromosomes exchanging DNA sequences when lined up during mitosis causing 2 mutant copies of the tumor suppressor gene to end up in the same cell

Question 47

explain gene conversion

Answer 47

base sequence information getting copied from one chromosome to another when they're lined up next to each other. causes the mutant tumor suppressor gene to be copied onto the normal chromosome

Question 48

explain hereditary Rb

Answer 48

offspring have a 50% chance of inheriting a defective Rb gene

Question 49

explain nonhereditary Rb

Answer 49

cancer only arises if both copies of Rb undergo mutations in the same cell

Question 50

Rb tumors are believed to arise from a

Answer 50

multipotent stem cell precurser of multiple types of cells

Question 51

name a type of human tumor suppressor genes that have been cloned

Answer 51

RB NF1

Question 52

NF1 is a _____ ______ of Ras signaling

Answer 52

negative regulator

Question 53

NF1 stands for

Answer 53

neurofibromatosis type 1

Question 54

neurofibromatosis type 1 is a

Answer 54

familial cancer precursor w/ an inherited mutant allele

Question 55

what forms around the cell sheaths of PNS?

Answer 55

neurofibromas form around cell sheaths of the PNS

Question 56

NF1 patients are at higher risk for

Answer 56

developing additional cancers

Question 57

what drives more than a quarter of breast cancers

Answer 57

missing gene