molecular oncogenesis

Question 1

What are the gene targest-regulatory genes that lead to cancer?

Answer 1

protooncogenes
-activation
tumor suppressor genes
-inactivation
antiapotptosis genes
-activation
apoptosis genes
-inactivation

Question 2

protooncogene is what?

Answer 2

a normal regulatory gene; inolved in regulating normal cell growth; expression under tight control

Question 3

What are oncogenes?

Answer 3

genes involved in autonomous unregulated cell proliferation in cancer cells
expression is constituitive

Question 4

What are growth factors?

Answer 4

tumors acquire to ability to produce GF to which they are responsive
may develop GF receptors
cell proliferation results in further growth factor

Question 5

What are the role of growht factor receptors as oncogenes?

Answer 5

normal transient activation; become oncogenes in overexpression or mutations ofr constituitive expression

Question 6

What is the ERB B2 (Her2-neu) role in cancer?

Answer 6

amplification in breast cancer
poor prognostic sign
unresponsiveness to estrogen therapy

Question 7

What is a the role of ras oncogene?

Answer 7

point mutation 15-20% of all tumors
GTP binding proteins with reduced GTPase activity
potential chemotherapy target

Question 8

What is the role of c-ABL gene in oncogenesis?

Answer 8

transient tyroisine kinase activity
t(9,22) philadelphia chromosome creates a er-abl fusion
chronic myelogenous leikemia and acute lymphoblastic leukemia
constituitive activity

Question 9

What are the role of transcription factor c-MYC in oncogenesis?

Answer 9

increased expression or mutation leads to different tumor

c-MYC overexpression translocation from 8-14 leads to Burkitt lymphoma

Question 10

What is the role of n-MYC geen in oncogensis?

Answer 10

amplification in neroblastoma(25-30%)
poor prognosis
leads to constant signal for proliferation

Question 11

What is the role of Rb protein in oncogenesis?

Answer 11

knock out of Rb lets cyclin D be constantly active instead of being witheld by Rb

Question 12

What is the role of Cyclin D1 in oncogenesis?

Answer 12

mantle cell lymphoma
t(11,14)
cyclin D1-IgH fusion leads to overexpression

Question 13

What is the retinoblastoma model?

Answer 13

mutation in both alleles for oncogenesis because it is a tumor suppressor gene
sporadic mutations lead to rare unilateral retinoblastoma
in familial retinoblastoma one abnormal gene more likely to occur in both eyes

“two-hit hypothesis”

Question 14

What is the APC gene?

Answer 14

gene involved in destruction and thus down regulation of Beta-catenin
APC mutation is a two hi leading to Beta-catenin accumulation complements with TFC and grwoth

most involved in familial adenomatous polyposis
greater than 100 mucosal polyps
prophylactic colectomy
APC mutation

Question 15

What is p53 function?

Answer 15

cell cycle arrest, intiation of apoptosis following DNA damage

Question 16

What is Li-Fraumeni syndrome?

Answer 16

p53 mutation that leads to many different cancers at a young age

Question 17

What is teh role of BCL2 inc ancer?

Answer 17

BCL2 is anti-apoptotic
overexpressed in many lymphomas
Especially follicullar lymphoma
t(14,18)–>overexpression

Question 18

What are the carcinogenic categories?

Answer 18

microbes/viruses
chemicals
radiation

Question 19

What are the two classifications of chemical carcinogenic compounds?

Answer 19

direct-acting carcinogens
-direct damage to dna

indirecct-actign carcinogens

• procarcinogen
• metabolism activates it

Question 20

What is the effect of a polymorphism of CYPIA1?

Answer 20

10% caucasians have highly inducible form; leads to increased carcinogens; involved in polycyclic aromatics increase cancer

Question 21

What is the effect of gutathione-S-transferase polymorphism?

Answer 21

50% of caucasians have deletion leading to increase cancer; lack of clearance

Question 22

What is a initator carcinogen chemical?

Answer 22

direct and indirect; permanent damage to DNA targets vs repaired targets

Question 23

What are promoter chemical carcinogens?

Answer 23

give a stimulus to cells to grow leading to increase cancer risk

Question 24

What are the two types of radiation that lead to cancer genesis?

Answer 24

ionizing radiation
-x-rays
-gamma rays
UV light
-UVA
-UVB
-UVC

Question 25

UV light leads to increase cancer so f what sort?

Answer 25

basal cell carcinoma, melanoma, and squamous cell carcinoma

formation of pyrmidine dimers

Question 26

What are the mechanisms of oncogenesis of most infectious diseases?

Answer 26

viral genomic integration

stimulation of host inflammatory response with subsequent regeneration

Question 27

What are hep B and hep C linked to as far as cancer?

Answer 27

chronic liver injury leading to regeneration; hepatocellular carcinoma
also HBx in hep B activates growth genes and inhibits p53

Question 28

What is H. pylori linked to in onocgenesis?

Answer 28

gastric adenocarcinoma and extranodal marginal zone lymphoma;
hot inflammatory response leads to carcinogenesis of adenocarcinoma
or polyclonal expansion may select for population with aditional mutations lymphoma MALToma

Question 29

What is BCR-ABL’s associated tumor?

Answer 29

CML ALL

Question 30

What is bcl-2’s related tumor?

Answer 30

follicular and undifferentiated lymphoma

Question 31

What tumor does BRAF cause?

Answer 31

melanoma

Question 32

What tumor does ckit caues?

Answer 32

Gastroinitestinal stromal tumor

Question 33

What tumor does cmyc cause?

Answer 33

Burkitt

Question 34

What tumor does HEr2 mutations cause?

Answer 34

breast, ovarian and gastric carcionam

Question 35

What tumor does Lmyc cause?

Answer 35

lung tumors

Question 36

What tumor does N myc cause?

Answer 36

neuroblastoma

Question 37

What tumor does ras cause?

Answer 37

colon cancer lung cancer pancreatic cancer