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MCDB 135(2) Cellular Oncogenes
Midterm 2
11
Biology
Undergraduate 4
11/13/2006

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Term
How Transfection led to discover of oncogenes
Definition
DNA is extracted from a cancer cell and placed in a CAP2 buffer. These crystals are placed on a monolayer (Phosphate helps with DNA incorperation) and injected into a host mouse. The mouse gets cancer
Term
erbB2/HER2/neu Oncogene
Definition
In breast cancer patients, a southern blot was taken to determine a connection between the oncogene and b.c Restriction enzyme fragments demonstrated breast carcinomas contained extra copies of the gene. According to the Kaplan Meier plot, patients with the extra copies of the genes were much less likely to survive more than 18 months after prognosis. [image]
Term
Multiple Gene Amplification
Definition
It is possible for an oncogene to amplify more than one of the genes that flank it in addition to itself. As demonstrated by the fluorescent imaging.
Term
How to determine genetic mutations between proto-oncogene and oncogene counterpart
Definition
The proto oncogene (h-ras) and the oncogene (human bladder carcinoma oncogene) were transfected and then tested for tumors. They were then cleaved and transfected again. This process was repeated until the oncogene genetic sequence was narrowed down to only 350 bp.
Term
Mutation responsible for the H-ras oncogene activation
Definition
After determining the 350 base pair fragment oncogene, the seqences were then determined for both the 350 bp oncogene and the 350 bp proto onco gene counter part. A single base pair change in the 12th codon is the only difference (gly-val)
Term
N-myc over amplification
Definition
Using Fluorescence in situ hybridization, it can be shown that children with neuroblastomas have increased levels of N-myc on their 8th chromosome.
Term
Other types of mutations that convert transcriptional Activators into Oncogenes
Definition
1) Mutations that allow transcriptional activators to bind DNA in the absence of an activating phosphorylation event
2) Mutations in gene regulatory sequences that increase the rate of expression of the transcriptional factor.
Term
Chromosomal Translocations
Definition
Chromosomal translocations in Burkitt's lymphoma cells result in overexpression of myc. This happens when the expression of the c-myc gene is placed under control of the transcription-controlling sequences of an immunoglobulin gene due to reciprocal chromosomal translocations. (8-14)[image]
Term
What Drives the 8-14 Chromosome switch in Burkitt's lymphoma
Definition
Antibody (immunoglobulin) gene rearrangement drives the exchange. Because the immunoglobulin enhancer sequences direct high, constitutive expression, the normal modulation of myc expression is increased. The resulting oncogene makes normal myc protein, but in excess amount. Further mutations may further potentiate the function of the myc oncoprotein. [image]
Term
bcr-abl tanslocation
Definition
Generates a fusion protein that is always active. Reciprocal chromosomal rearrangments between 9 and 22 result in a fusion protein that is constituitively active. [image]
Term
Oncogenetic phenotype characteristics
Definition
Dominant transforming phenotype. A sigle copy is usually able to transform a cell and/or generate tumors even though a wild type copy is present

Oncogenes are more likely to be found as somatic rather than germline mutations.

Currently roughly 200 oncogenes exist.

A sequence of 14,000 human genes revealed that more than 400 of those are overexpressed in tumor cells.
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