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Are oncogenes gain or loss-of-function?
GOF
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Does a GOF function dominantly or recessively?
Dominant
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How does the RAS oncogene function?
- RAS generally binds GTP to activate growth
- After time, RAS is hydrolyzed by GAP (like NF1) to hydrolyze GTP and inactivate
- When RAS is an oncogene, it cannot hydrolyze the GTP so it is always on, even in the absence of a mitogen
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How does MYC act as an oncogene?
- MYC is not mutated
- 1) Active promoter: more transcription of MYC RNA
- 2) Increased gene copies: multiple on one chromosome, MYC gene amplified
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What is Burkitt's lymphoma?
- ***Ebstein-barr virus, HIV
- translocation b/t chromo. 8 &14
- 14 has an active promoter
- Transcription increased from single gene
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How does MYC amplification work?
- DNA problems can cause multiple MYC genes to appear on chromosomes
- Normal mRNA but from multiple genes (leads to more protein)
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What is the philadelphia chromosome?
chromosome 9 and ABL coming together with chromosome 22 and BCR
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What does the Philadelphia Chrom. produce? How?
- CML (leukemia)
- ABL is generally a tyrosine kinase
- When ABL-BCR the TK is constantly active
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What is clonal expansion?
- Mutated cells replicating self
- over time causes higher mutations and more chance of cancer
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What are the 3 phases of tumor growth?
- 1) initiation
- 2) promotion
- 3) pogression
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What is 1) initiation?
mutation with potential
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What is 2) promotion?
proliferation of mutated cells only (not normal cells)
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What is 3) Progression?
- oncogene + inactivated tumor suppressor
- benign to malignant
- No tumor promoter required
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Initiation or Promotion: Cigarette Smoke and Alcohol??
- Cigarette Smoke: initiator
- Alcohol:
promoter
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What causes Angiogenesis?
- Cell lacks oxygen and nutrients
- Releases growth factors (VEGF)
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When is a tumor malignant?
When it has chewed through the basal lamina and began to protrude into underlying tissue
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What chemical is used by the malignant tumor to chew through the basal lamina?
Matrix Metalloproteinases (MMP)
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How does a cell travel to a new place? (Seed and Soil)
- Initiate, Promote, and Progress
- MMP to break basal lamina
- enter blood and lymph
- MMP to break into new cell
- **Certain cells are very picky about their soil so they only metastasize to certain places.
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