So, cancer develops multiple mutations, and these mutations accumulate in one cell, which allows for the creation of cancer, which is a commonly known fact. That is how cancers form. Now, there are 2 classes of mutations. There are passenger mutations, and these are mutations that have accumulated but have no direct contribution to the cancer. They're not resulting in growth, proliferation, or stopping apoptosis. There's a lot of DNA damage, and some of that is going to be in regions that have nothing to do with the cancer at all. So those are the passenger mutations. Then we have the driver mutations, and these are the ones that are driving the cancer. They are causing the cancer cell, giving the cancer cell some way to grow abnormally, proliferate abnormally, or stop death abnormally. The driver mutations are really the ones that are causing the cancer. But the passenger mutations are just kind of along for the ride, which is why they're named that way.
Now, within the driver mutations, there are 2 more classes. These are the 2 most common ones. The first is called oncogenes. An oncogene is a mutated allele. Normally, this is usually a normal allele, but now it's mutated and acts dominantly. That means that if it's mutated, you're going to see some type of phenotype, and that phenotype is going to be cancerous. The normal version of that gene is called a proto-oncogene. That's the wild type version, the unmutated version. When those proto-oncogenes are mutated, they become oncogenes. It's important to understand the difference between proto-oncogenes and oncogenes, as this is often a question on an exam.
Examples of oncogenes that you may read about include Ras GTPase, which is an important one in a signal transduction pathway. But also, viruses like E6, when mutated or integrated into the genome. The second class is tumor suppressors, which function exactly opposite to oncogenes. These alleles have a normal function, and their normal function is to stop cell division. When they become mutated, they can no longer stop cell division. Tumor suppressors' normal function is to suppress tumors. So when they're mutated, they lose that function and can no longer suppress them.
Examples of these include retinoblastoma, which is the transcription factor that, when mutated, stops suppressing the tumor and allows those tumors to proliferate. Another one is p53, which is also a transcription factor, whose normal function is to suppress tumors. But when it's mutated, it can no longer do that, allowing tumors to grow. A lot of tumor suppressors are transcription factors that regulate many genes. It's not just affecting one. So when p53 becomes mutated, it means that every gene that it regulates is also being not expressed correctly; it's either being over expressed or underexpressed. This creates a huge phenotype from just one mutation in the p53 gene or the retinoblastoma gene.
Interestingly, mutations in p53 and retinoblastoma are generally accumulated in somatic cells, so they are not inherited. For retinoblastoma, it can be inherited. It's a major cause of a certain type of eye cancer in children and it can definitely be inherited. These generally act as recessive alleles, and you need both copies to be mutated before you see the phenotype, especially in retinoblastoma. That's the case.
So essentially, what happens here is you have a proto-oncogene, and it's normal, but some type of cancer-causing agent comes in, activates it, meaning that it creates some type of mutation in it. This, with the accumulation of other cancer mutations, will lead to cancer. Make sure you understand the difference between oncogenes and tumor suppressors because you will 100% see questions on the difference between the two. So with that, let's now move on.
