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mcdb135 Tumor suppressor
midterm 2
18
Biology
Undergraduate 4
11/14/2006

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Term
Experimental fusion of cancer
Definition
When cells (one normal and one cancer) growing next to one another are exposed to a fusogenic agent such as polyethylene glycol, they form a hetrokaryon with multiple nuclei. After the tetraploid cell divides, if the hybrid cell is tumorigenic, then cancer alleles are dominant(usually in case of virus induced), if hybrid is non tumorigenic, then the cancer alleles are recessive (mutagens)
Term
Oncogenes vs. tumor suppressor genes
Definition
Oncogenes are dominant transforming phenotype. (gain of function) A single mutation event causes oncogene to stimulate cell proliferation

Tumor suppresor genes are recessive mutations. Need two mutation events to eliminate t.s gene...stimulating proliferation
Term
Retinoblastoma
Definition
Childhood eye tumor. Unilateral means one eye affected and there us no risk of further cancers

Bilateral is familial and means increased risk later in life. It is easier to detect earlier in life
Term
Rb genetics
Definition
In order for Rb to create a tumor, both alleles must be mutated because it is a recessive trait.(unilateral) However, in familial, the defective Rb gene is already present in the germ line and therefore only a single mutation even needs to take place anywhere in the retina to initiate uncontrolled proliferation. [image]
Term
Elimination of wt Rb gene copies
Definition
Mitotic recombination can leah to LOH. of a gene. Genetic material is exchanged between two homologous chromosomes. during crossing over in the g2 phase. After segregation of the chromatids at mitosis, there is equal probability that there will be an LOH of ROH [image]
Term
LOH Mechanism 2
Definition
Gene Conversion.

This can occur when DNA polymerase begins on one chromosome for DNA replication and jumpes over to the homolog and continues replication, and jumps back. This can lead to LOH
Term
Deletion Mapping of TS genes
Definition
Darkly staining bands on specific parts of the chromosome made it easy to identify the karyotype of Rb patients.
Term
Genetic Markers used to Map TS genes
Definition
When a known gene is present next to a TS gene, test for the known gene in both cancer and non cancer patients
Term
Restriction Lengh polymorphisms
Definition
Genetic markers that are known to cleave or not when applied to a restriction enzyme.
Term
PCR mapping
Definition
Can be used to determine a single polymorphism. The Primers on the alleles must match, if the primer fails to bind completely, there is no elongation and PCR will not proceed.
Term
DNA methylation
Definition
In cytosine/guanine sequences, certain genes can be shut off through the use of methylation, which can be just as important as mutation.
Term
NF1 Protein
Definition
Expressed widely throughout the body. Forms negative feedback with the ras gene
Term
Haploinsufficieny
Definition
Reduction in protein level due to loss of one gene copy
Term
APC
Definition
ABC is a tumor suppresor gene that can be associated with Familial Adenematous Polyposis (FAP) colon cancer, and is located in the kinetochores

Loss of APC also leads to Chromosome instability (anneuploidy)
Term
VHL
Definition
Tumor suppresor gene that acts in kidney cancer. Also acts as a ubiquitin ligase for that targets transcription factor HIFa for degradation. Under normal conditions pVHL can bind to HIF and prevent excessive transcription by ubiquitation and degradation. Disfucntional VHL gene allows for uncontrolled VEGF transcription.
Term
BRCA1 and 2
Definition
Function in DNA damage checkpoints and DNA repair. Mutations in these genes are associatied with breast and ovarian cancer.
Term
MLH1
Definition
Mutations in MLH1 can lead to microsatellite instabilty

1) A microsatellite is a sequence of DNA consisting of tandem one or two base repeats

2) Succeptible to additional duplications if MRH! is not present (mismatch repair genes)

3) often associated with hereditary non polypsosis colon cancer
Term
p27kip1
Definition
Acts both early and late to suppress carcinogenesis.

1 Early - Precents the transition from G1 to s in absence of mitogenic stimulation

2 Late - Blocks metastasis. Inactivates microtuble regulator stathmin, which promotes disassembly, allowing reorganization of actin cytoskeleton which is prereq to migration.
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