Lecture 8 - Tumor Suppressor Genes Flashcards
What is a tumor suppressor gene? What has to happen for phenotypes to appear in an individual? What are some of the pros/cons to this kind of thing for cancer?
Tumor suppressor genes are genes that influence the development of cancer if they are “lost” impaired/mutated or generally deleted/silenced… wtv
Both copies of an individual’s tumor suppressor gene need to be “lost” before phenotypes appear. In other words, carriers are ok until they lose the second copy… then shit hits the fan.
Pros: easier to inactivate genes than to hyperactivate them
Cons: requires a double knockout, two seperate genetic alterations (low probability: 1x10^6 per copy)
Describe the cancer fusion experiments. What are some of the possible outcomes (4) and list what they mean.
In the cancer fusion experiments, two cells (regular or cancerous) were fused in different combination with one another in order to observe the possible genetic outcomes.
Outcomes:
1 - Syncytium: one cell, multiple distinct nuclei
2 - Polykaryon: too much genetic material in 1 cell
3 - Homokaryon: both bad copies in one daughter cell
4 - Heterokaryon: dominant/recessive
2,3,4 were when a normal cell was fused with a cancerous one.
In 1, either two cancerous or two normal cells were fused.
What is retinoblastoma. What are the two types. Give details as to timing, inheritability, and anything else you can remember about this thing at this point.
Retinoblastoma is the formation of tumors in the retina. It is inheritable and can be either sporadic or familial.
If sporadic, it is said to be unilateral (1 eye) and typically occurs later on when the host is older. This is said to be a two-hit model since the host has to spontaneously lose both copies of the gene. After you lose the first, you become much more susceptible to losing the second.
If familial, it is said to be bilateral (both eyes) and usually occurs very early on when the child is still young. Here, the individual is born with one mutated copy of the gene. It is said to be a one-hit model as a single mutation can trigger the phenotype (you only have one good copy left).
Basically, retinoblastomas form in the presence of a defective Ras gene.
What are the two categories for inherited tumor suppressor genes? Can oncogenes be inherited?
1 - Gatekeepers:
allow cell to grow and progress through the cell cycle
2 - Caretakers:
maintain the integrity of the cellular genome ex: by monitoring recombination repair, etc…
Oncogenes CANNOT be inherited.
How do you inactivate a tumor suppressor gene? What are Cpg islands?
In order to inactivate tumor suppressor genes, the promoter before the gene in question is methylated (through mutation, oncogenic signalling pathway etc…)
This then inhibits the transcription of the tumor suppressor gene.
Cpg stands for Cytosines 5’ to Guanosines. Cpg islands are termed as regions of DNA hypermethylation in certain cell regions/tissues. In DNA samples taken from distant, nearby, and upstream to the actual tumor cells, histone deacetylases (HDAC’s) were continously attracted to increasing degrees in relation to proximity to the tumor. Being upstream is the worst since you are dealing with the promoter = highest Cpg/methylation activity.
Basically… this means that the DNA can no longer be accessed and the tumor suppressor gene is effectively “lost”.
How do you tell the difference between tumor suppressor genes and oncogenes?
Use a zygote experiment. If you are dealing with a tumor suppressor gene, typically half ot the zygote cells will develop normally.
If you are dealing with an oncogene, there is not way you’ll get past the 100 cell range. The zygote won’t develop under the constitutively active protein expression/overtranscription of genes. The hyperactivity and overstimulation will spell death.
How can you test for this? What is a probe?
Using a DNA probe (complimentary to the tumor suppressor gene/promoter in question) you can observe levels of methylation in relation to the promoter of the gene.
If incredibly high/Cpg islands = you’ve got bad news.
