Created by Tracy Kim Kovach.
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- Does Khan Adacemy advise the memorization of these oncogene examples for the 2014 MCAT?(26 votes)
- When I took my mcat I don't remember ever having to learn specific oncogenes. Just had to understand what they were(46 votes)
- i understand the knowledge and time needed to make a video. Unfortunately, this video does not follow the traditional format of khan academy videos. For example, I feel like the presenter is only writing what I can find in the textbook. Draw more pictures less text please. This video didn't do anything for me.(39 votes)
- My understanding is that proto oncogene direct normal cell growth, and oncogenes are the cancer causing counterparts, at0:06, tracy says that oncogenes normally direct cell growth? am i missing something?(23 votes)
- I think what she is trying to say by "normally direct cell growth" is that the proto-oncogene, which does indeed direct normal cell growth, is the normal version of the oncogene. The proto-oncogene controls cell growth, and when the proto-oncogene is mutated/moved/etc. it is no longer normal and becomes an oncogene.(5 votes)
- I'm more confused than I was before, haha, guess I will go to another webpage to try to wrap my head around this tumor :P(8 votes)
- What do you mean by hyperactive? (at around1:45) Hyperactive sounds similar to overexpression(3 votes)
- The result is the same, mechanism is different. Hyperactive means literally over-active. A protein may be able to continually activate downstream signals without being activated itself. Overexpression means that the gene is overly-expressed. There are way too many copies of the protein being created, which could be bad if the protein's role is to make the cell divide.(6 votes)
- I feel that I haven’t got the difference between oncogenes and tumor suppressor genes right!
Oncogenes mutations happens spontaneously and never inherited? and I suppose it’s dominant?
On the other hand, tumor suppressor mutations can be inherited and it’s recessive, it only inherits the preparation for the disorder and it needs another mutation that happens spontaneously?
Am I right?
Is there any other difference that matters?(2 votes)
- According to the American Cancer Society:
"An important difference between oncogenes and tumor suppressor genes is that oncogenes result from the activation (turning on) of proto-oncogenes, but tumor suppressor genes cause cancer when they are inactivated (turned off)."
Again according to the ACS: "most cancer-causing mutations involving oncogenes are acquired, not inherited" — this makes sense since inheriting one of these mutations would probably result in very early death, perhaps even a miscarriage.
Yes, it sounds like mutations in oncogenes are (usually) dominant (I can't promise there aren't exceptions).
Your description of tumor suppressors sounds correct, but the ACS claims that most of these mutations are also spontaneous.
- what is the t(9;22) notation? I understand that the BCR-ABL fusion protein results from a chromosomal translocation occurring with chromosomes 9 and 22, but I've never seen the t(9;22) notation before and I'd like clarification? Does the t just mean translocation? Are there similar notations for related concepts that I should be aware of?(3 votes)
- Does the MCAT require us to know those specific examples shown at6:13in red or are we okay with just understanding the concept and general theme of oncogenes and what causes them.(2 votes)
- don't know about MCAT exactly, but these [examples in red] are all classic examples of the main types of (proto)oncogenes and are worth being familiar with.
it's always good to have an example in mind to back up what you're talking about, whether it's a receptor tyrosine kinase overexpression (HER2), translocation carcinogenesis (t(8:14) in burkitt's lymphoma), or tumour suppressor gene inactivation (p53), etc.(2 votes)
- HOw would the chromosomal rearrangement if you fused a segment of the DNA into another portion of the DNA result in the increase in output of the normal protein in high quantities?(1 vote)
- Well chromosomal rearrangement may place the structural gene downstream of a more active promoter resulting in more active translation. Alternatively, rearrangement may place a gene right next to another structural gene. The end product would be a fused protein that for some reason is more active, not necessarily over expressed.(3 votes)
Voiceover: Oncogenes are genes that code for proteins that normally direct cell growth. They start out as proto-oncogenes and then something happens to convert that proto-oncogene into a full blown oncogene and that's in some sort of tumor-inducing agent or it could also be totally spontaneous. Now proto-oncogenes code for proteins that help to regulate cell growth and differentation which makes sense since the essence of a tumor, whether it is a cancerous or a benign one, is unregulated cell growth. In fact, the words oncogene and oncology, which is the study of cancer, share the same root word, onkos, which is Greek for mass or bulk. Now the products of these genes are often involved in signal transduction and the execution of mitogenic signals. And you should recall that a mitogen is a chemical substance that encourages a cell to start cell division, basically something that triggers mitosis. So how does a proto-oncogene make that switch into an oncogene? Well, there are three main mechanisms, deletion or point mutation, gene amplification or increased mRNA stability, and chromosomal rearrangement. So let's start with the first one. Deletion or point mutation in coding sequence of the DNA in the gene itself or within a regulatory region such as a promoter region can lead to either a protein that is produced in the same normal amounts but is hyperactive for some reason or maybe there's some sort of loss of regulation and the normal protein is just overexpressed. Gene amplification or an increase in mRNA stability that prolongs the existence of the mRNA and thus its activity in the cell can lead to a normal protein that is overexpressed. And then finally, chromosomal rearrangement involves translocation of a gene to a nearby regulatory sequence that then causes this normal protein, the gene product, to be overexpressed or you could possibly have fusion to an actively transcribed gene which overexpresses the fusion protein or leads to a hyperactive fusion protein. And so really you can start to see a theme here emerging where the key idea is that you have either a normal protein that is just overexpressed, basically too much of the normal protein or you can have normal expression but the protein itself is just a hyperactive one. Now there are tons of examples of oncogenes including the SRC oncogene, RAS, MYC, receptor tyrosine kinase, and also cytoplasmic tyrosine kinases. So let's talk about each one of those here. SRC was the first confirmed oncogene which was discovered in 1970, and was termed SRC for sarcoma, which is a tumor of mesenchymal cells or connective tissue cells. It was actually an oncogene discovered in a chicken retrovirus and so SRC codes for a nonreceptor protein tyrosine kinase so it phosphorylates specific tyrosine residues and other proteins. Another example of an oncogene is the RAS oncogene, which codes for a small GTPase which hydrolyzes GTP into GDP and phosphate. This protein is activated by growth factor signaling and functions like a binary switch, sort of an on/off switch, in growth signaling pathways. Examples of downstream effectors of RAS includes the protein MAPK, which is a type of kinase that in turn regulates genes that mediate cell proliferation. You can see examples of RAS oncogene mutations In thyroid tumors, certain leukemias, and cancers of the pancreas and colon. The MYC oncogene codes for a transcription factor that induces cell proliferation and there's a very common translocation involving MYC between chromosomes 8, where the MYC oncogene is found, and 14, which leads to a certain type of lymphoma called Burkitt's lymphoma. The RTK oncogene stands for receptor tyrosine kinase, which is responsible for adding phosphate groups to other proteins to turn them on or off. These are similar to the SRC gene which is a non-receptor tyrosine kinase, the difference being the location of the protein, either at the cell surface as a receptor or not as a receptor. So say you have a cell surface receptor that receives a signal from outside of the cell. Well, then that signal gets propagated or transmitted Into the cell via these receptor tyrosine kinases that add phosphate groups to the target protein, specifically on tyrosine residues and they can cause cancer by turning a receptor constitutively or permanently on in the absence of signals from outside the cell. Some well known examples of receptor tyrosine kinases are vascular endothelial growth factor or VEGF, epidermal growth factor or EGFR, and platelet derived growth factor, PDGF. And finally we have the cytoplasmic tyrosine kinases, which mediate responses to the activation of receptors of cell proliferation, migration, differentiation, and survival. A well known example is the BCR-ABL gene in chronic myelogenous leukemia or CML, also known as the Philadelphia chromosome. It is a fusion of parts of DNA from chromosome 22 and chromosome 9. So basically a part of chromosome 22 which contains the BCR gene fuses with a fragment from chromosome 9 which contains the ABL gene. When these two chromosome fragments fuse, the genes also fuse, creating this new gene, the BCR-ABL gene. The fused gene codes for a protein that displays high protein tyrosine kinase activity, which is actually due to the ABL half of the protein and the unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which causes a cell to grow and divide uncontrollably, basically becoming cancerous. So as a result, the Philadelphia chromosome is associated wtih chronic myelogenous leukemia, a certain type of leukemia as I mentioned before, as well as other forms of leukemias, which are cancers of white blood cells.