Neoplasia: Tumor Supressor Gene

Question 1

Tumor suppressor gene with intact oncogene

Answer 1

Quiescence

Question 2

Permanent cell cycle arrest rather than uncontrolled proliferation

Answer 2

Senescence

Question 3

Tumor suppressor genes activity

Answer 3

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

Question 4

Those 3 activity of TSG originates outside the cells and use

Answer 4

Receptors
Signal transducers
Nuclear transcription regulation

Question 5

First TSG discovered

Answer 5

RB or retinoblastoma gene

Question 6

Prototype of gene of this type

Answer 6

RB

Question 7

Familial RB

Answer 7

40%

Autosomal dominant

Question 8

10,000 folds

Answer 8

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

Question 9

60%

Answer 9

Occur sporadic

One eye only

Question 10

Occurence of RB

Answer 10

Two hit hypothesis of oncogenesis

Question 11

Pathogenesis of RB

Answer 11

2 mutations of RB focus on chromosome 13q14

Question 12

Both RB mutation in tumor retinal cell acquired

Answer 12

Sporadic form

Question 13

All somatic cells inherit one mutated copy of RB gene

Answer 13

Familial form

Question 14

In familial case first hit

Answer 14

Inherit one defective copy of the RB gene

Question 15

Second hit

Answer 15

Spontaneous somatic mutation

1 RB mutated in retinoblastoma

Question 16

Sporadic two hit point

Answer 16

Both RB must undergo somatic mutation in the same retinoblast

Question 17

Genetic trait associated with germ line mutation in RB

Answer 17

Autosomal

Question 18

Loss of function mutations in the RB gene

Answer 18

Recessive

Question 19

Child is normal if carrying

Answer 19

Inherited mutant RB in all somatic cell

Question 20

Inhibitor of mitogenic signaling pathways

Answer 20

APC
NF1
NF2
PTCH
PTEN
SMAD2
SMAD4

Question 21

Inhibitor of cell cycle progression

Answer 21

RB

CDKN2A

Question 22

Inhibitor of RAS/MAPK signaling

Answer 22

NF1

Question 23

Inhibitor of WNT signaling

Answer 23

APC

Question 24

Inhibitor of PI3K /AKT signaling

Answer 24

PTEN

Question 25

Inhibitor of G1/S

Answer 25

RB

Question 26

P16 P14 Indirect activator of p53

Answer 26

CDKN2A

Question 27

Cell cycle arrest and apoptosis in response to DNA damage

Answer 27

TP53

Question 28

Activator of AMPK family of kinases

Answer 28

STK11

Question 29

Cell adhesion' inhibition of cell motility | Altering cell metabolism

Answer 29

STK11

Question 30

Genomic stability

Answer 30

BRCA1 and BRCA2

Question 31

Governor of proliferation

Answer 31

RB

Question 32

RB loss of function

Answer 32

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

Question 33

RB gain of function

Answer 33

Up regulate CDK/cyclin D | Inactive hyper phosphorylated state

Question 34

Complexes lead to hyper phosphorylation and inhibition of RB

Answer 34

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

Question 35

Up regulate activity of CDK/cyclin

Answer 35

Growth factor signaling pathway

Question 36

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

Answer 36

Other RB family exist that may partially complements RB function

Question 37

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

Answer 37

Other genes can mimic the effect of RB loss

Question 38

Guardian of the genome

Answer 38

TP53

Question 39

Most frequent mutated gene in human cancers

Answer 39

TP53

Question 40

TP53 regulates

Answer 40

Cell cycle progression DNA repair Cellular senescence Apoptosis

Question 41

Loss of function of TP53 located on

Answer 41

Chromosome 17p13.1

Question 42

3 leading cause of cancer death, Tp53

Answer 42

Lung Colon Breast

Question 43

Somatic cells not inherited in germ lines

Answer 43

Inheritance of TP53

Question 44

Inheritance of TP53

Answer 44

Only one additional hit

Question 45

Li fraumeni syndrome

Answer 45

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

Question 46

Stimulate the degradation of p53

Answer 46

MDM2 and family

Question 47

Viral oncoprotein that binds to p53 that promote degradation

Answer 47

E6 protein

Question 48

Kapag na disrupt o hindi nag bind si MDM2 at p53

Answer 48

Mac aacumulate si p53 which is good

Question 49

Paano a di disrupt ang binding ng MDM2 at p53

Answer 49

``` DNA damage ( ATM and ATR) Oncogenic stress ( ARF binds to MDM2) dispalce p53 ```

Question 50

Once activated p53 induced

Answer 50

Cell cycle arrest Senescence Programmed cell death

Question 51

Successful repair

Answer 51

P21 (CDk inhibitor) | GADD 45

Question 52

Transient p53 induced cell cycle arrest

Answer 52

CDKN1A to CDK inhibitor p21 | GADD45

Question 53

Decrease CDK =

Answer 53

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

Question 54

Increase CDK4 =

Answer 54

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

Question 55

Encodes a factor that negatively regulates the WNT

Answer 55

APC

Question 56

Colon carcinomas

Answer 56

APC

Question 57

Contact mediated growth inhibition of epithelial cells | Signaling protein that functions in the WNT pathway

Answer 57

E Cadherin

Question 58

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

Answer 58

CDKN2A

Question 59

Potent inhibitor of cellular proliferation

Answer 59

TGF beta pathway

Question 60

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

Answer 60

PTEN

Question 61

Encodes neurofibronmin 1 | A gtpase that acts as a negative regulator of RAS

Answer 61

NF1

Question 62

Encodes neurofibronmin 2 (merin) | Cytoskeletal protein in contact inhibition

Answer 62

NF2

Question 63

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

Answer 63

WT1

Question 64

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

Answer 64

PTCH1

Question 65

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

Answer 65

VHL

Question 66

Recognizes genotoxic stress and shutting down proliferation

Answer 66

RB | P53