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Pathology Midterms > Neoplasia: Tumor Supressor Gene > Flashcards

Neoplasia: Tumor Supressor Gene Flashcards

1
Q

Tumor suppressor gene with intact oncogene

A

Quiescence

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2
Q

Permanent cell cycle arrest rather than uncontrolled proliferation

A

Senescence

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3
Q

Tumor suppressor genes activity

A
  1. Growth inhibitory pathways
  2. Pro-differentiation
  3. Mitogenic signals
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4
Q

Those 3 activity of TSG originates outside the cells and use

A

Receptors
Signal transducers
Nuclear transcription regulation

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5
Q

First TSG discovered

A

RB or retinoblastoma gene

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6
Q

Prototype of gene of this type

A

RB

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7
Q

Familial RB

A

40%

Autosomal dominant

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8
Q

10,000 folds

A

Carriers of RB
Both eyes
Develop osteosarcoma and other soft tissue sarcoma

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9
Q

60%

A

Occur sporadic

One eye only

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10
Q

Occurence of RB

A

Two hit hypothesis of oncogenesis

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11
Q

Pathogenesis of RB

A

2 mutations of RB focus on chromosome 13q14

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12
Q

Both RB mutation in tumor retinal cell acquired

A

Sporadic form

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13
Q

All somatic cells inherit one mutated copy of RB gene

A

Familial form

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14
Q

In familial case first hit

A

Inherit one defective copy of the RB gene

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15
Q

Second hit

A

Spontaneous somatic mutation

1 RB mutated in retinoblastoma

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16
Q

Sporadic two hit point

A

Both RB must undergo somatic mutation in the same retinoblast

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17
Q

Genetic trait associated with germ line mutation in RB

A

Autosomal

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18
Q

Loss of function mutations in the RB gene

A

Recessive

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19
Q

Child is normal if carrying

A

Inherited mutant RB in all somatic cell

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20
Q

Inhibitor of mitogenic signaling pathways

A 
APC
NF1
NF2
PTCH
PTEN
SMAD2
SMAD4
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21
Q

Inhibitor of cell cycle progression

A

RB

CDKN2A

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22
Q

Inhibitor of RAS/MAPK signaling

A

NF1

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23
Q

Inhibitor of WNT signaling

A

APC

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24
Q

Inhibitor of PI3K /AKT signaling

A

PTEN

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25
Q

Inhibitor of G1/S

A

RB

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26
Q

P16
P14
Indirect activator of p53

A

CDKN2A

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27
Q

Cell cycle arrest and apoptosis in response to DNA damage

A

TP53

28
Q

Activator of AMPK family of kinases

A

STK11

29
Q

Cell adhesion’ inhibition of cell motility

Altering cell metabolism

A

STK11

30
Q

Genomic stability

A

BRCA1 and BRCA2

31
Q

Governor of proliferation

A

RB

32
Q

RB loss of function

A

Mutation involving both RB alleles
Mutation that end CDK inhibitors
Active hypo phosphorylated

33
Q

RB gain of function

A

Up regulate CDK/cyclin D

Inactive hyper phosphorylated state

34
Q

Complexes lead to hyper phosphorylation and inhibition of RB

A

CDK 4/ cyclin D
CDK 6/ cyclin D
CDK 2/ cyclin E

35
Q

Up regulate activity of CDK/cyclin

A

Growth factor signaling pathway

36
Q

Why do patients with germ line RB mutations preferentially develop only a few type of cancer?

A

Other RB family exist that may partially complements RB function

37
Q

Why mutations of RB are not more widespread in human tumors?

A

Other genes can mimic the effect of RB loss

38
Q

Guardian of the genome

A

TP53

39
Q

Most frequent mutated gene in human cancers

A

TP53

40
Q

TP53 regulates

A

Cell cycle progression
DNA repair
Cellular senescence
Apoptosis

41
Q

Loss of function of TP53 located on

A

Chromosome 17p13.1

42
Q

3 leading cause of cancer death, Tp53

A

Lung
Colon
Breast

43
Q

Somatic cells not inherited in germ lines

A

Inheritance of TP53

44
Q

Inheritance of TP53

A

Only one additional hit

45
Q

Li fraumeni syndrome

A

Develop cancer at young age
25 folds
Malignant tumor by 50 yo

46
Q

Stimulate the degradation of p53

A

MDM2 and family

47
Q

Viral oncoprotein that binds to p53 that promote degradation

A

E6 protein

48
Q

Kapag na disrupt o hindi nag bind si MDM2 at p53

A

Mac aacumulate si p53 which is good

49
Q

Paano a di disrupt ang binding ng MDM2 at p53

A 
DNA damage ( ATM and ATR)
Oncogenic stress ( ARF binds to MDM2) dispalce p53
50
Q

Once activated p53 induced

A

Cell cycle arrest
Senescence
Programmed cell death

51
Q

Successful repair

A

P21 (CDk inhibitor)

GADD 45

52
Q

Transient p53 induced cell cycle arrest

A

CDKN1A to CDK inhibitor p21

GADD45

53
Q

Decrease CDK =

A

Loss of function
Active hypo phosphorylation
Blocked G1 phase to s phase

54
Q

Increase CDK4 =

A

Gain of function
Inactive hyper phosphorylation
Proceed G1 phase to S phase
RB inhibition

55
Q

Encodes a factor that negatively regulates the WNT

A

APC

56
Q

Colon carcinomas

A

APC

57
Q

Contact mediated growth inhibition of epithelial cells

Signaling protein that functions in the WNT pathway

A

E Cadherin

58
Q

Suppressive proteins, p16/ INK4a a cyclin dependent inhibitor that augment RB function and ARF which stabilize p53

A

CDKN2A

59
Q

Potent inhibitor of cellular proliferation

A

TGF beta pathway

60
Q

Encodes a lipid phosphatase that is an important negative regulator of PI3K/AKT

A

PTEN

61
Q

Encodes neurofibronmin 1

A gtpase that acts as a negative regulator of RAS

A

NF1

62
Q

Encodes neurofibronmin 2 (merin)

Cytoskeletal protein in contact inhibition

A

NF2

63
Q

Encodes a transcription factor that is required for normal development of genitourinary tissues

A

WT1

64
Q

Encodes membrane receptor that is a negative regulator of the Hedeghog signaling pathway

A

PTCH1

65
Q

Encodes a component of a ubiquitin ligase that is responsible for degradation of hypoxia induced factors

A

VHL

66
Q

Recognizes genotoxic stress and shutting down proliferation

A

RB

P53

Pathology Midterms (5 decks)

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