Molecular Genetics of Cancer

Question 1

Mutations of tumor suppressors are mainly what kind of cellular component?

Answer 1

transcription factors

Question 2

an oncogene is mutated via point mutation is usually known as a?

Answer 2

gain of function mutation

Question 3

What is the only naturally occurring growth factor oncogene?

Answer 3

sis

Question 4

What does sis encode for?

Answer 4

PDGF

Question 5

Polycythemia vera and Erythroleukemia are mutations involving what receptor mutation?

Answer 5

gp55

Question 6

HPV is inappropriately stimulated by what receptor?

Answer 6

E5 leading to sustained activation of PDGF receptor

Question 7

Non-muscular tropomyosin is involved with what chromosomal translocation?

Answer 7

Trk receptor kinase

located in the cytosol after change

Question 8

Many breast cancers are due to ?

Answer 8

HER2 gene over expression

Question 9

Treatment of HER2+ breast cancer

Answer 9

Herceptin=only extend life expectancy by 5 mo

Question 10

What induces GTP hydrolysis of the Ras?

Answer 10

GAP

Question 11

What has the capability of activating Ras?

Answer 11

SOS has GEF activity

Question 12

Ras then can activate the what pathway that phosphorylates what 3 things in order?

Answer 12

RAF>MEK>ERK

Question 13

What amino acid is changed to convert Ras into an oncogene?

Answer 13

postion 12 amino acid to GLY=leaves RAS active

Question 14

C-Src is normally activated at Tyr position at C-term 527 by?

Answer 14

de-phosphorylation

Question 15

In Rous Sarcoma, Src has a deletion at terminal?

Answer 15

C-term position 18 producing v-Src and leaving it active

Question 16

C-Fos and c-Myc are

Answer 16

transcription factors

Question 17

What phase of the cell cycle does c-myc and and c-for encode genes for?

Answer 17

Progression through G1 and G1 to S phase

Question 18

Burkitt’s lymphoma where is the c-myc gene translocated from and to where?

Answer 18

CH 8 to CH 14

Question 19

What does the c-myc translated gene use to encode its protein products?

Answer 19

antibody enhancer

Question 20

High expression and localized duplication of the translocated myc gene can

Answer 20

lead to increased expression of myc

Question 21

Non-Hodkin’s Lymphoma aka

Answer 21

Burkitt’s lymphoma

Question 22

folicular lymphoma involves

Answer 22

a translocation of bcl2 gene on CH 18 that fuses together with an antibody enhancer on CH 14

Question 23

bcl2 in Burkitt’s lymohoma is produced by antibody enhancers causing

Answer 23

increase in anti-apopotosis

Question 24

What would increase the cell cycle abnormally?

Answer 24

point mutation to a cyclin or loss of tumor supressor

Question 25

Tumor suppressors involved for the restriction point in G1 pathway?

Answer 25

p16 and Rb

Question 26

TGF beta is

Answer 26

a tumor suppressor

Question 27

TGF beta induces p15 that leads to the synthesis of what

Answer 27

collagens and PAI-1

Question 28

Tumor cells display the following qualities

Answer 28

``` increased metabolic activity enhanced glycolysis suppressed OPP high NAs, fatty acid, and proteins glutamine addicted ```

Question 29

Glutamine is necessary for what specifically in tumor cells?

Answer 29

replenished the intermediates of TCA cycle

Question 30

In a normal cell with DNA damage, what is activated by the DNA damage>

Answer 30

p53

Question 31

What is then in turn secreted by this activated substance that responds to DNA damage?

Answer 31

TIGAR inhibits F 2,6 BSP from stimulating PFK1 and PGM inhibits GA3P DH rxn

Question 32

What is a necessary enzymes for the PPP in the oxidative run?

Answer 32

G6PD and NADP+ reducing to NADPH

Question 33

R5P will stimulate

Answer 33

GA3P and F6F

Question 34

In tumor cells, the oxidative pathway is blocked, via tumor enzymes

Answer 34

PKM2 and TKTL1

Question 35

PKM2 acts to

Answer 35

let glycolytic intermediates build up and increase in flux through the non-oxidative pathway

Question 36

TKTL1 GA3P and F6P to

Answer 36

R5P in the non-oxidative pathway to create DNA and RNA

Question 37

F1,6BP inhibits

Answer 37

the oxidative pathway inhibiting G6P

Question 38

If there is a mutattion at p53, what will happen to glycolysis

Answer 38

there will be less NADPH produced from the PPP due decreased inhibition of the glycolytic pathway

Question 39

Glycolysis depends on the recycling go what?

Answer 39

NAD+

Question 40

Glutamine will do what

Answer 40

replenish the TCA cycle with necessary intermediates and produce NADPH

Question 41

Important intermediates for anoploetic rxns

Answer 41

Malate>>>lactate citrate>>>fatty acid syn Alpha keto gluterase for protein syn

Question 42

VDAC bound to HK-2 bound to ATP where and prevents what ?

Answer 42

it is located on the Mitochondrial membrane and prevents the release of apoptosis inducing factor and used to make G6P for the PPP and Pyruvate Pathway

Question 43

Warburg effect is basically

Answer 43

Increase in glycolysis decrease in OP increase in lactate production

Question 44

To kill cancer we must

Answer 44

``` induce necrosis-----inhibit HK2 induce apoptosis-----release AIF decrease the pH in cell inhibit lactate release increase the ROS ```

Question 45

3-bromopyruvate

Answer 45

modifies HK2 so it cannot bind VDAC and AIF is released and necrosis insures ATP stores depleted

Question 46

HIF-1alpha

Answer 46

increases glycolysis and decreases OP | essential for metabolic changes for cancer

Question 47

Cancer in summary

Answer 47

Hexokinase II and pyruavte kinase M2 up regulated OP decreased (PDH unregulated to keep pyruvate out out of MIT) the non-oxidative part of PPP increase due to TKL1 and PKM2 Glutamine upregulated more ROS generated fatty acid syn, protein syn upreglated