The Cancer Genome Flashcards
what are proto-oncogenes involved in?
synthesis of receptors
synthesis of messenger systems
involved in nuclear transcription
what are oncogenes? effect on function? effect on cell cycle? how many alleles need to be impacted? end result?
oncogenes = "gain-of-function" encodes proteins stimulates cell cycle needs mutation in 1 copy of allele (one hit process) creates more active protein
what are tumor suppressor genes? effect on function? effect on cell cycle? how many alleles need to be impacted? end result?
tumor suppressors = "loss-of-function" encodes proteins inhibits cell cycle needs mutation in both copies of allele (two hit process) creates no active proteins
what are clastogens responsible for?
structural alterations that occur when chromosomes are broken
what %age of CA is due to viruses?
20%
EBV, HBV, NCV, HTLV-1, HPV, HHV-8, MCPyV
5 classes of proto-oncogenes?
- EC growth factors
- growth factor receptors
- IC signal transducers
- nuclear transcription factors
- tumor suppression genes
what are EC growth factors?
homologs of normal growth factors
what are growth factor receptors?
membrane proteins that capture EC signals stimulating cell growth
what are IC signal transducers?
transmit signal initiated by growth factor binding to receptors
what are transcription factors?
regulate gene expression
what are tumor suppression genes?
negative regulators of cell growth
proto-oncogene associated with breast CA?
HER2/neu (ERB2) - amplification of this gene leads to BrCA
defective RET gene leads to what? what mutation has occurred?
point mutation in RET gene leads to MEN IIa, IIb
defective RAS gene leads to what? what mutation has occurred?
point mutation of RAS gene leads to colon CA, pancreatic CA and leukemia (GTP signal transduction receptor dysfunction)
defective ABL gene leads to what? what mutation has occurred?
translocation of ABL gene leads to 9,22 CML (tyrosine kinase activity, non-receptor function)
diseases that result from receptor synthesis mutations?
breast CA and MEN IIa, IIb
diseases that result from messenger system mutations?
colon CA
pancreatic CA
leukemia
9,22 CML
diseases that result from nuclear transcription mutations?
8,14 Burkitt’s Lymphoma
Neuroblastoma
defective c-MYC gene leads to what? what mutation has occurred?
nuclear transcription mutation of c-MYC receptor leads to 8,14 Burkitt’s Lymphoma
defective n-MYC gene leads to what? what mutation has occurred?
nuclear transcription mutation of n-MYC receptor leads to neuroblastoma
examples of compounds that are considered epigenetic carcinogens but which have not shown mutagen activity?
diethylstilbestrol
arsenite
hexachlorobenzene
nickel compounds
what is DNA methylations impact on gene transcription?
DNA methylation is an important regulator of gene transcription - aberrant DNA methylation is associated with unscheduled gene silencing
what is the activity of genes with high levels of 5-methylcytosine in their promoter region?
transcriptionally silent
impact of hypermethylation? typically occurs where?
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
importance of H2A.X (histone variant)?
marks DNA damages, facilitates recruitment of DNA repair problems to restore genomic integrity
importance of H2A.Z (histone variant)?
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
what has been shown in regards to epigenetic pharmaceuticals and their potential effect on proto-onco regions and tumor suppressor sequences?
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
what is unique about epigenetics that could also play a big role in CA therapy?
epigenetics can be reversible - something other chemo txs do not have the potential for
what is HAT and HDAC? significance of HDAC?
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
tumor marker for colon CA? for liver CA? for pancreatic CA? for ovarian CA? for testicular CA? for prostate CA? for breast CA?
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
