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Flashcards in Cancer Deck (98):
1

A disease in which a single cell escapes normal control over growth and division, and proliferates without limit

Cancer

2

Any abnormal new growth of cells

-Can compete with normal cells for nutrients

Tumor or Neoplasm

3

Tumors (neoplasms) can be either

Benign or Malignant

4

Non-cancerous tumor. It is localized and does not spread

-can cause secondary problems

Benign tumor

5

Cancerous tumors that resist treatmens, can spread to other parts of the body, and may recur after removal

Malignant Tumor

6

Most cancer-causing mutations are

-occur post fertilization

Somatic

7

Mutagens are mostly environmental. The most important are

Smoking and Viral infections

8

What are two common viral causes of cancer, which are responsible for 30-50% of worldwide cancer cases?

Human papilloma and Hepatitis B and C

9

Multiple mutations are required to cause

Cancer

10

Typically about a dozen signal-transduction pathways are altered in a

Tumor cell

11

Lose the ability to respond to ECM and neighboring cell signals

Cancer cells

12

Normal cells will cease division when they come into contact with neighboring cells. This is called

Contact inhibition

13

Normal cells do not survive or divide in the absence of signals from the

Extracellular matrix

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Are immune to contact inhibition

Cancer cells

15

In cancer cells, detachment from other cells and invasion of neighboring tissue is promoted by

Loss of cadherins

16

Not dependent on signals from the ECM for cell division

Cancer cells

17

Cancer cells secrete metalloproteases that degrade the ECM and facilitate

Tissue invasion

18

Mutations in which three classes of genes underlie most cancers?

1.) Caretaker genes
2.) Gatekeeper genes
3.) Oncogenes

19

Its products prevent or repair damage to DNA

Caretaker genes

20

Is not oncogenic itself, but promotes further genetic change/increases chance

Loss of caretaker protein function

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Its products restrain cell division or induce apoptosis if cells initiate division when they should not

Gatekeeper genes

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Loss of gatekeeper protein allows

Uncontrolled proliferation

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Its products promote cell growth and division

Oncogenes

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Mutations in these genes do not inactivate their proteins, but cause loss of normal control, so that continuous activity drives cell division

Oncogenes

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Were discovered as genes mutated in inherited cancer syndromes (e.g. Ptc1 in medulloblastoma)

Tumor suppressor genes

26

Loss-of-function mutations inactivate

Tumor suppressor protein

27

Are recessive, meaning both functional copies must be lost to cause a cell to become cancerous

Tumor suppressor genes

28

In pedigrees, tumor suppressor gene mutations appear

Dominant (even though they are actually recessive)

29

Caretaker genes prevent or repair DNA damage, what are three examples?

1.) MLH
2.) ERCC1
3.) BRCA-1/2

30

Gatekeeper genes restrict cell division. What are the two most important?

1.) Rb
2.) p53

31

Inhibits the G1/S transition by inhibiting E2F

Rb

32

Halts cell division or initiates apoptosis in response to DNA damage or other stress

p53

33

Mutations in caretaker genes cause

Familial cancer syndromes

34

Mutations in MLH cause lynch syndrome which is associated with defects in which repair pathway?

Mismatch repair

35

Mutations in ERCC1 result in Xeroderma pigmentosum. This is associated with defects in which repair pathway?

NER

36

Mutations in BRCA-1/2 result in familial breast/ovarian cancer. This is associated with defects in which repair pathway?

Double-strand break repair

37

Loss of function mutations in Rb cause retinoblastoma. What are the two forms of the disease?

1.) Sporadic retinoblastoma
2) Familial (inherited) retinoblastoma

38

Single tumors in one eye of one person in a family

Sporadic retinoblastoma

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Tumors are often bilateral and often multiple family members are affected

Familial retinoblastoma

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Which occurs at a younger age on average, familial or sporadic retinoblastoma?

Familial

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In retinoblastoma, the tumor replaces the retina. As a result, the pupil appears

White

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Follow the curve expected if two events are required for tumor formation

Unilateral Rb tumors

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Follow the curve expected if only one event is required for tumor formation

Bi-lateral Rb tumors

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How many mutations are required to acquire sporadic Rb?

Two (because it is a recessive disease)

45

How many mutations are required to acquire familial Rb?

One

46

If one defective copy of a tumor suppressor gene is inherited, it is likely that the second copy will be inactivated. This is called

Loss of Heterozygosity (LOH)

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Loss of p53 renders cancer cells immune to

Apoptosis

48

The most commonly mutated protein in human cancers

p53

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p53 stimulates transcription of

1.) Cdk inhibitors
2.) pro-apoptotic proteins

50

Intrinsically unstable, but is stabilized in response to DNA damage

p53

51

p14ARF (ARF = alternate reading frame) stabilizes

p53

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p53 is stabilized by ARF and destabilized by

MDM2

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ARF binds MDM2 and frees p53. Thus, as far as cell death is concerned, ARF is considered to be

Pro-apoptotic

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Cell stress activates a p53 modification that blocks

MDM2 binding

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In un-stressed cells, p53 is destroyed by

-a ubiquitin ligase
-anti-apoptotic

MDM2

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p53 has no defined tertiary structure unless it is bound to

DNA

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Destabilize p53's DNA binding domain, blocking its apoptotic activity

Oncogenic mutations

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A gene that can cause cancer when activated or expressed

Oncogene

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A normal gene that can turn into an oncogene as a result of mutations or increased expression

Proto-oncogene

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Discovered in retroviruses, which insert a DNA copy of its genome into host-cell DNA

Oncogenes

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Viral oncogenes are originally derived from the genome of the

Host cell

62

Lead to continuous (constitutive) activity of the protein, unaffected by normal regulatory mutations

-gain of function mutations

Oncogenic mutations

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Gain-of-function mutations show which type of heredity?

Dominant

64

Family of tyrosine kinase proteins with SH2 domains that transduce signaling through various Protein Kinase receptors

Src (c-Src is a proto-oncogene)

65

NF1 (a ras-GAP), Cdk inhibitor, and Rb are all considered to be

Tumor suppressor proteins

66

The mTOR pathway is frequently mutated in

Tumors

67

Promotes cell growth downstream of growth-factors

-a proto-oncogene

mTOR pathway

68

What is the kinase that converts PIP2 to PIP3?

PI3K

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What is the phosphatase that converts PIP3 back to PIP2

PTEN

70

A protein kinase activated in the presence of PIP3 that phosphorylates and inhibits TSC

AKT (PKB)

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An inhibitor of mTOR

-mutations cause tuberous sclerosis in CNS, kidney, heart, and lung

TSC

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A protein kinase that phosphorylates multiple targets to promote protein synthesis and cell growth

mTOR

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What are three examples of activation of oncogenes?

1.) c-myc
2.) c-abl
3.) c-ras

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Promotes expression of about 15% of human genes

-Activated by overproduction

c-myc

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Genetic change allows self-activation so normal regulatory stimuli are no longer required

c-abl

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Mutations prevent inactivtion

c-ras

77

In some tumors, the number of gene copies of c-myc is

Increased (gene amplification)

78

Increase expression of c-myc can also be the result of a

Chromosomal translocation

79

If copies of c-myc remain in the chromosome, they form a

-whole chromosome glows in FISH

Homogenously-staining region (HSR)

80

In c-myc amplification, the c-myc genes may also be found outside of the chromosome in tiny

double-minute chromosomes

81

When chromosomes break and rejoin crosswise

Translocation

82

Alterson transcriptional control of c-myc by placing the gene under the control of a powerful promoter

Translocation of c-myc

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A tumor of B lymphocytes that results from c-myc activation

Burkitt Lymphoma

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In Burkitt lymphoma, the transcription of antibody genes is driven by powerful

B-cell enhancers

85

When translocations put c-myc under control of an antibodygene enhancer and the c-myc gene is transcribed at many times the normal rate

Burkitt Lymphoma

86

Results from a a translocation which results in constitutive activity of the protein kinase c-abl

Chronic Myelogenous leukemia (CML)

87

The karyotype of Chronic Myelogenous leukemia (CML) shows a chromosome known as the

"Philadelphia Chromosome"

88

In CML, there is a reciprocal translocation between

-results in 1 large chromosome and 1 "Philadelphia chromosome"

Chr9 and Chr22

89

One of the most frequently altered proteins in human tumors

Ras

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Binds guanine nucleotides

-Active when GTP is bound
-Inactive when GDP is bound

Ras

91

Ras has slow intrinsic GTPase activity that is stimulated by

GAPs

92

A ras-GAP in which mutations result in neurofibromatosis (tumors of peripheral nerves)

NF1 protein

93

What are 4 examples of proteins containing ras homology domain?

1.) Translation factors
2.) Large G-proteins
3.) Dynamins
4.) Myosin and Kinesin

94

Translation factors such as the aminoacyl-tRNA binding to ribosomes and the translocation of peptidyl-tRNA contain

Ras homology

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Transduce signals from 7-α-helix receptors

Large G-proteins

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Proteins that function in the budding of membrane vesicles

Dynamins

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Most oncogenic mutations in Ras are amino acid substitutions at which two positions?

gly-12/13 and gln-61

98

If mutations in many genes are required to initiate cancer, how can a single drug with presumably a single cellular target block cancer progression?

"oncogene addiction" i.e. some tumors come to rely on one dominant oncogene, which can then be targeted by drugs

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