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NEU Genetics Fall 2010 Lec 25
These flashcards cover most lecture and slide material from Vollmer's genetics section lecture #25
21
Microbiology
Undergraduate 1
11/30/2010

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Cards

Term
What are some general properties regarding cancer?
Definition

Cancer is not a single disease but an umbrella term for similar diseases which typically have some form of uncontrolled growth. Only 1% of all cancers are familial contrary to popular belief. Tumor cells are colonial which means that they all originated from one single cell that became cancerous

Term
What is contact inhibition and what is its role in cancer?
Definition

Contact inhibition is the process by which cells come into contact with each other and know that that is when they should stop cell division. In cancer cells they don't recognize the contact inhibition signals and continue to undergo more and more cell division

Term
How do normal cells and cancer cells compare with each other on a molecular level?
Definition

Normals cells stop dividing once they've undergone about 50 doublings (this is called cell senescence) due to the degredation of their telomeres via a loss of telomerase activity. Cancer cells have very high levels of telomerase which help them to avoid cell senescence

Term
What sort of genetic alterations are typically needed to induce cancer?
Definition

Mutations within the cell cycle regulatory genes are necessary for cancer to develop. The most common step that is mutated with adverse effects is the G1-S transition. These alterations also affect apoptosis through their interactions with the p53 gene. Usually multiple mutations are needed to cause cancer

Term
What exactly are proto-oncogenes?
Definition

Proto-oncogenes are genes which, under normal, non-cancerous conditions, promote cell division or prevent apoptosis. These genes need only one mutagenic hit to become oncogenes (cancer genes)

Term
What are tumor supressor genes?
Definition

Normal functions of tumor supressor genes are to prevent cell divison or to promote apoptosis. These genes need two hits to potentially become cancerous.

Term
What will happen if an individual is heterozygous for a proto-oncogene mutation?
Definition

The individual will develop excessive cell profileration in the negative allele and will likely develop cancer if that cell is not destroyed by other means

Term
What will happen if an individual is heterozygous for a tumor-supressor gene?
Definition

The individual will not develop excessive cell proliferation since there is still a safety net in the form of the other wildtype allele. Remember: tumor-supressor genes require mutations in both alleles to have a real chance at becoming cancerous

Term
What happens when the oncogene Mdm2 is overexpressed?
Definition

Amplification of the Mdm2 gene and expression of the Mdm2 protein leads to the inactivation of the p53 gene

Term
What effect do the oncogenes Cyclin D and CDK4 have when overexpressed?
Definition

Amplification and overexpression leads to unscheduled entry into the S phase

Term
What effect do mutations in the oncogene classification of growth-factor receptors have?
Definition

Amplification and overexpression promotes uncontrolled cell growth

Term
How does the oncogene Ras work and what are its effects?
Definition

Ras acts as a switch in stimulating cellular growth in the presence of growth factors. Ras mutants lack GTPase activity and remain stuck in active form (Ras-GTP) which automatically transmits the signal for cell growth and unrestricted cell growth ensues

Term
What happens when two mutations to the p53 gene occur?
Definition

Loss of function eliminates the DNA checkpoint that monitors DNA damage in G1 and S. The damaged cells survive and proliferate with their genetic instability which increases the chances of further genetic changes and thus progression towards a cancerous state. More and 50% of all cancers have non-functioning p53

Term
What happens when the TSG p21 suffers a loss of function?
Definition

Loss of the p21 function results in renewed rounds of DNA synthesis without mitosis and the level of ploidy in the cell increases

Term
What is the relationship between p16/p19ARF and what do they do?
Definition

These genes are products of the same gene but are initiated by different promoters. The p16 product can inhibit the cyclin D-CDK4 complex and help control entry into S phase

Term
How does the TSG retinoblastoma work and what does a loss of function mutation result in?
Definition

RB controls the transition from G1 to S by controlling the activity of the transcription factor E2F. Loss of RB function frees the E2F and the cell will go into excessive rounds of DNA synthesis which are continuously being initiated

Term
Why might the Bax TSG become mutated?
Definition

Loss of Bax function is typically due to microsatellite instability because of defective mismatch repair

Term
What is the Bub1 TSG involved in?
Definition

Bub1 is involved in the spindle checkpoint. If the spindle fibers aren't properly attached Bub1 will be activated and anaphase is either aborted or delayed

Term
What is Li-Fraumeni Syndrome?
Definition

LFS shows clear autosomal dominant inheritance for cancer. However, individuals have a range of different tumors and often have more than one. p53 mutations are very common and have been replicated in the germ cells of mice

Term
What did Alfred Knudson suggest in regards to retinoblastoma?
Definition

Since RB is a TSG people who are heterozygous for the mutant allele will only need one hit to develop the cancer. If one mutant allele is present in a family line then it is possible to reduce the hit factor to one

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