Proto-Oncogenes & Mechanisms of Oncogene Activation – Carcinogenesis

00:01 Here we will take a look at proto-oncogenes. Always go back and take a look at that flow chart so that you know exactly as to where you are located. That is your roadmap to carcinogenesis.

00:12 And at some point in time when you read a GPS you always want to kind of want to know where you began from and where you end up. And at this point we are looking at proto-oncogenes and before we get into actual carcinogenesis understand that proto-oncogenes are things that we require. For proper normal cellular growth. For example, as an embryo and a foetus our brain develops. We can't do that on our own. We need the help of proto-oncogenes.

00:41 Now imagine that you have the development of cancer. This is unregulated, not supervised growth of cells.

00:51 So what do you think happens to the proto-oncogenes. It gets mutated and then it becomes a oncogene.

00:56 What's the name of a specialty that, maybe a clinician such as yourself in the future will go into? An oncologist.

01:06 So here genes that actually form oncology or the practice of cancer. So what's the mechanism of action that you want to be familiar with. We will dive into great detail about RAS. And before we get into that I want to make sure that you understand a proper organization method that I will be setting up for you. You will be looking at growth factors and when the time is right I will talk to you about certain growth factors that are associated with certain cancers that you must know. Growth factors bind to please? Receptors, good. And those receptors will then communicate with whom? Signal transducers that are located where? On the inside aspect of your membrane. Where are you now? In the cytoplasm and from the cytoplasm you are then going to communicate with and to the nucleus.

01:58 And within the nucleus you require certain transcription factors and obviously certain oncogenes that are able to then tell the DNA to continue replicating without stop. I'll show you where RAS is located in that journey.

02:15 The translocations, example here will be something like t(8;14). So now at this point I would like for us to expand upon the translocation or specifically chromosome 14. Really important for us. Now to begin with, take a look at the parenthesis here. There is no such thing as an IgH, alright. There is an IgG, IgA, IgM, IgE, IgD but there is no such thing as IgH. So what does that H stand for. I want you to think of the anatomy of an immunoglobulin.

02:44 And in Immunology you learned about that there is a heavy chain and light chain. Well it's the heavy chain that you are focusing upon here, specifically with chromosome 14. Hence, the IgH.

02:55 Now whenever you see the chromosome 14 in any type of cancer that you are associated with including t(8;14), t(11;14) and t(14;18), guess what they all contain an immunoglobulin heavy chain. Versus what Dr. Raj? Versus light chains. You have heard of multiple myeloma. You have heard of IgG and IgA. And with multiple myeloma you have heard of Bence-Jones proteins. Those are your light chains and that would be kappa and lambda, we'll obviously talk about that in WBC pathology. So what you are looking at here is a normal chromosome on your left 8 and 14. Perfectly normal. They are not sharing at all any particular components of the chromosome.

03:39 Then what then happens with Burkitt lymphoma is the fact that there is a translocation of 8 upon 14.

03:45 And now at this point you have an oncogene next to IgH. Excuse me. Better said as immunoglobulin heavy.

03:52 I want to make sure we are clear. So when you have an oncogene next to an immunoglobulin heavy chain guess what you are going to do.

03:59 You are going to create an abundance of immunoglobulin heavy chain. Welcome to Burkitt lymphoma. And with Burkitt lymphoma, I want to make sure that we reinforce over and over again, you will be responsible for two types. You'll have the endemic type and the non-endemic type. The endemic type is the type that you will find in Africa. Non-endemic type will be the type that most likely will be found in North America. We'll take a look at gene amplification. This is when you have a messenger down in the nucleus that is able to then cause or instruct a DNA to never stop replicating.

04:36 An example for this would be something like MYC as well. But this one is N-myc with neuroblastoma.

04:42 I'll summarise all this for you when we get into actual growth factors and such.