QUESTIONS AND CORRECT DETAILED ANSWERS
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Oncogenes in Cancer - CORRECT ANSWER- Aberrant expression of proto-oncogenes that
increases cell proliferation/survival
First identified in cancer-causing viruses
Typically a dominant mechanism
Oncogene activation is usually limited to somatic tissue, but more cases of inherited oncogene
mutations are being found
Biochemical functions of oncogenes - CORRECT ANSWER- G-proteins (Ras)
Protein Kinases (Raf, Akt)
Lipid Kinases (PI3-Kinase)
Transcription Factors (Myc)
Binding and inactivating apoptotic proteins (BCL2)
Protein Kinase regulatory subunits (Cyclins A, E, D)
Transcriptional coactivators (B-Catenin, YAP, TAZ)
,Five Ways to Activate Oncogenes - CORRECT ANSWER- 1. Mutation of gene to make it
overactive
2. Amplification of a normal gene
3. Chromosomal Rearrangement
4. Promoter/enhancer insertion
5. Hypomethylation of oncogene
Amplification - CORRECT ANSWER- Multiple gene copies = too much transcript and protein
DNA sequencing, DNA-PCR
RNA sequencing, RNA-PCR
Protein: Western
Chromosomal Rearrangement - CORRECT ANSWER- Affects regulatory region of oncogene
Cytogenetics
PCR using primers
Oncogene - CORRECT ANSWER- A gene that causes or contributes to the development of
cancer
Hallmarks of Cancer - CORRECT ANSWER- Sustaining proliferative signaling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative immortality
Inducing angiogenesis
Resisting cell death
, In vivo oncogenic evidence - CORRECT ANSWER- Cause cancer when activated in a transgenic
animal
Render nontumorigenic cells tumorigenic
Knock down or knock out in tumorigenic cells renders the cells nontumorigenic
Activation/overexpression of the oncogene is strongly correlated with human cancer
In vitro oncogenic evidence - CORRECT ANSWER- Causes anchorage-independent growth in
soft agar (protection from anoikis)
Causes focus formation (loss of contact inhibition)
Renders cell growth factor independent
Promoter/Enhancer Insertion - CORRECT ANSWER- From retroviral integration near oncogene
Gene expression activated from the viral promoter
Should activate oncogenes or disrupt tumor suppressors
Can find new genes
Hypomethylation of Oncogenes - CORRECT ANSWER- Ex. N-ras is activated in liver cancer due
to under-methylated promoter, allowing gene expression
Directly measure methylation using methyl-sensitive restriction enzyme/genomic DNA,,
bisulfite genomic sequencing, or methylation specific PCR
measure RNA/protein level
Oncogenes in medical practice - CORRECT ANSWER- Specific diagnosis, sub-classification of
tumor type, and/or prognosis can be based on certain gene involvement
EGFR Inhibitors - CORRECT ANSWER- Sustaining proliferative signaling