00:01
Although cancer is not necessarily heritable, on occasion it is. It is certainly a genetic disorder.
00:11
Let’s take a look into the root of cancer. You’re probably all quite familiar already with the progression
and metastasis of cancer from physiology. But what sorts of things do result in cancer?
We know that they are mutations of genes. But let’s ask ourselves the question, what kind of genes
end up resulting in cancer? Think about that for just a moment. First of all, it would certainly
have to be genes. You probably recall talking about p53 and genes like that in cell cycle controls.
00:50
So, any gene that has anything to do with cell cycle control, cell proliferation, or even cell death
because if cell death goes awry then clearly we’re having cells around when they shouldn’t be around.
01:04
Usually, they might be around or they should have been gone through apoptosis because they have
some damage to them. Although very few cancers are heritable, they are certainly genetic
but most arise from sporadic mutations. Those mutations generally occur in the somatic cells.
01:28
For a cancer to be heritable, that mutation has to occur in a germline cell. That’s much more rare
than say, regular cancer cells of the somatic kind. In any tumor though, one thing that we probably
don’t think about too often, we’re taught so often that the cells are all alike and sort of undefined,
but the truth is the cells of a cancer are all fairly heterogeneous. Once one mutation occurs
which initiates the cancer then many other mutations will follow, such that the cells are much more
heterogeneous in a tumor than we may have previously thought. We break these mutations
into two types of mutations. On one hand, we have the passenger mutations or passenger genes.
02:21
These are the ones that seemed to be affected after the initial cancer has developed,
whereas the other class that we’re really interested in are these driver genes. They’re the ones that are
in control of the whole initial mutation. The passenger genes will happen as a result of these
driver gene mutations. They are involved in the disease progression itself. Again, we ask ourselves,
what kind of mutations are these driver genes? Pretty much anything you can associate
with cell proliferation and cell cycle control and apoptosis are potential targets. Why don’t you
for just one moment pause and write down all the things that you think or you might remember
that are involved in cell cycle controls, apoptosis, and cell proliferation, cell growth. Take a moment.
03:24
Write those things down. Then let’s visit and see if you have a pretty complete list. Naturally, I’m sure
you took into consideration the cell cycle and all of these checkpoints. Cell cycle control checkpoints,
you’ll recall the majority of them involve a cyclin and a CDK4 pairing. We have a variety of different
pairings at all three of these checkpoints. The M checkpoint, before we go into mitosis or meiosis,
should it be a germline cell. The G1 checkpoint, we want to make sure that the cell is prepared
and ready to go into DNA synthesis. We have a checkpoint at the end of synthesis also. I’m sure that
you came to the conclusion that some of these genes are involved in cell cycle controls.
04:19
Now, in cell biology and molecular genetics, we definitely went into quite a lot of detail on each of these
checkpoints involving a pairing of a cyclin and a CDK, right? Each of these different pairings will signal
the cell to go into the next stage of division. Each of these proteins are coded for by genes on the DNA.
04:39
We have various checkpoints throughout the cell cycle at which any mutation could cause
some kind of issue in cell cycle controls resulting in uncontrolled cell division. Cancer is uncontrolled
cell division, right? So, anything that lends itself to that. Here’s a quick summary
of all of the different mutations. Again, we have a very busy table of information
which you could certainly print out and take a more detailed look at. The point here is not to go through
the details of each of these mutations. We’ve covered the mechanisms of some before,
again in the molecular course. But just to sort of cap over all the sorts of mutations that could happen,
so anything involved in cell cycle regulation, right? Here are all these different checkpoints
that we could consider, all the different proteins, receptor tyrosine kinases, and growth factors,
and G proteins and anything involved in any of those protein cascades involved in the cell cycle
and cell proliferation. Cell differentiation, any of the factors involved in those, transcription factors
that will determine certain cell lineages as well as any genes that control apoptosis, so anything that is
regulating when a cell dies. Remember that there are gatekeeper genes and caretaker genes
that will check the DNA and send signals of whether that cell is healthy to move on to a next generation
or whether that cell should be destroyed and not allowed to proliferate. Any of these points
in cell development and life could lead to a cancer if there is a mutation and anyone of the proteins.
06:31
You can imagine there are literally thousands if not tens of thousands of possibilities in cell cycle
controls for things to go wrong. Another area of mutations that we need to consider in controlling
cell cycle are DNA integrity and the rates of gene expression. First of all, genome
and all the sorts of proteins that are involved in the genome integrity as well as those involved
in the rates and regulation of gene expression. Finally, all these epigenetic factors, what things
are involved, what proteins are involved in assuring that we get the right DNA methylation
in the right place and how do these regulate the gas and brake pedals of cell division
or cell cycle controls. Anyway, a number of different areas, again lots of details in the table.
07:31
You don’t need to sort of memorize all of these things. Just have a general understanding of all the sorts
of mutations that could lead to broken cell cycle controls because inevitably that’s what cancer is, right?