The Cancer Genome

Question 1

what are proto-oncogenes involved in?

Answer 1

synthesis of receptors
synthesis of messenger systems
involved in nuclear transcription

Question 2

what are oncogenes? effect on function? effect on cell cycle? how many alleles need to be impacted? end result?

Answer 2

oncogenes = "gain-of-function"
encodes proteins
stimulates cell cycle
needs mutation in 1 copy of allele (one hit process)
creates more active protein

Question 3

what are tumor suppressor genes? effect on function? effect on cell cycle? how many alleles need to be impacted? end result?

Answer 3

tumor suppressors = "loss-of-function"
encodes proteins
inhibits cell cycle
needs mutation in both copies of allele (two hit process)
creates no active proteins

Question 4

what are clastogens responsible for?

Answer 4

structural alterations that occur when chromosomes are broken

Question 5

what %age of CA is due to viruses?

Answer 5

20%

EBV, HBV, NCV, HTLV-1, HPV, HHV-8, MCPyV

Question 6

5 classes of proto-oncogenes?

Answer 6

1. EC growth factors
2. growth factor receptors
3. IC signal transducers
4. nuclear transcription factors
5. tumor suppression genes

Question 7

what are EC growth factors?

Answer 7

homologs of normal growth factors

Question 8

what are growth factor receptors?

Answer 8

membrane proteins that capture EC signals stimulating cell growth

Question 9

what are IC signal transducers?

Answer 9

transmit signal initiated by growth factor binding to receptors

Question 10

what are transcription factors?

Answer 10

regulate gene expression

Question 11

what are tumor suppression genes?

Answer 11

negative regulators of cell growth

Question 12

proto-oncogene associated with breast CA?

Answer 12

HER2/neu (ERB2) - amplification of this gene leads to BrCA

Question 13

defective RET gene leads to what? what mutation has occurred?

Answer 13

point mutation in RET gene leads to MEN IIa, IIb

Question 14

defective RAS gene leads to what? what mutation has occurred?

Answer 14

point mutation of RAS gene leads to colon CA, pancreatic CA and leukemia (GTP signal transduction receptor dysfunction)

Question 15

defective ABL gene leads to what? what mutation has occurred?

Answer 15

translocation of ABL gene leads to 9,22 CML (tyrosine kinase activity, non-receptor function)

Question 16

diseases that result from receptor synthesis mutations?

Answer 16

breast CA and MEN IIa, IIb

Question 17

diseases that result from messenger system mutations?

Answer 17

colon CA
pancreatic CA
leukemia
9,22 CML

Question 18

diseases that result from nuclear transcription mutations?

Answer 18

8,14 Burkitt’s Lymphoma

Neuroblastoma

Question 19

defective c-MYC gene leads to what? what mutation has occurred?

Answer 19

nuclear transcription mutation of c-MYC receptor leads to 8,14 Burkitt’s Lymphoma

Question 20

defective n-MYC gene leads to what? what mutation has occurred?

Answer 20

nuclear transcription mutation of n-MYC receptor leads to neuroblastoma

Question 21

examples of compounds that are considered epigenetic carcinogens but which have not shown mutagen activity?

Answer 21

diethylstilbestrol
arsenite
hexachlorobenzene
nickel compounds

Question 22

what is DNA methylations impact on gene transcription?

Answer 22

DNA methylation is an important regulator of gene transcription - aberrant DNA methylation is associated with unscheduled gene silencing

Question 23

what is the activity of genes with high levels of 5-methylcytosine in their promoter region?

Answer 23

transcriptionally silent

Question 24

impact of hypermethylation? typically occurs where?

Answer 24

one of the major epigenetic modifications that repress transcription via promoter region of tumor suppressor genes
typically occurs at CpG islands in the promoter region and is associated with gene inactivation

Question 25

importance of H2A.X (histone variant)?

Answer 25

marks DNA damages, facilitates recruitment of DNA repair problems to restore genomic integrity

Question 26

importance of H2A.Z (histone variant)?

Answer 26

plays an important role in gene activation and repression
high level so H2A.Z expression is ubiquitously detected in many cancers and is significantly associated with cellular proliferation and genomic instability

Question 27

what has been shown in regards to epigenetic pharmaceuticals and their potential effect on proto-onco regions and tumor suppressor sequences?

Answer 27

it has been shown that the epigenetic control of proto-onco regions and tumor suppressor sequences by conformational changes in histones directly affects the formation and progression of cancer

Question 28

what is unique about epigenetics that could also play a big role in CA therapy?

Answer 28

epigenetics can be reversible - something other chemo txs do not have the potential for

Question 29

what is HAT and HDAC? significance of HDAC?

Answer 29

drug that has focused mainly on histone acetyltransferase (HAT) and histone deacetylase (HDAC)
HDAC has been shown to play an integral role in the progression of oral squamous cancer

Question 30

tumor marker for colon CA?
for liver CA?
for pancreatic CA? 
for ovarian CA?
for testicular CA?
for prostate CA?
for breast CA?

Answer 30

colon CA - CEA
liver CA - AFP
pancreatic CA - CA 19-9
ovarian CA - CA 125
testicular CA - beta-HCG
prostate CA - PSA
breast CA - BRCA1/2