Yesterday I talked about Cancer Hallmark #3 ‘Resisting Cell Death’ and introduced a very important gene that encodes a protein called P53 which acts the guardian of the genome. I now realized maybe I need to back up a bit. So, here my best attempt at Genetics 101 as it relates to cancer.
DNA is the code or instruction manual for your body. Short segments of DNA are called genes and genes instruct your body to build proteins. Long segments of DNA that include multiple genes are organized into chromosomes. So…for size and on an organizational level…DNA < Genes < Chromosomes
Humans have 23 individual chromosomes and 22 of them have a matching pair (the 23rd chromosome pair is the XY or XX pair that determines sex) for a total of 46 chromosomes. You get one chromosome in each pair from your biologic mom and one chromosome in each pair from your biologic dad. Each egg and each sperm in the human body has half of the chromosome (23) and when they combine to form a fertilized egg, then there is a full set of 46 chromosomes that are carried forward into every cell and this also means you have two copies of each gene in every cell. Redundancy is a good thing here.
If the egg or sperm is carrying a mutation in a gene, then every cell in the body of the resultant person that formed from that egg and sperm will have that mutation. This is called a germline mutation. This type of mutation can be one the parent already knows they have or it can be something new that only exists in that particular egg or sperm (chromosomes doing some shuffling when eggs and sperm are made). This germline mutation is the type of mutation that is talked about a lot in regards to breast and ovarian cancer risk with the BRCA mutation (think Angelina Jolie).
So how do germline mutations relate to cancer? Well as I said yesterday, P53 is really important in protecting the body from tumor formation by monitoring what happens with cells. Its various functions, like activating apoptosis to get rid of bad cells, make it a TUMOR SUPPRESSOR…catchy name right? Anyway, most of the time it takes “two hits” to a gene pair in a cell before a problem happens because one good copy can usually do the heavy lifting and this is a good protection mechanism for the body. However, when you have a germline mutation, then you are born with ‘one hit’ to the gene pair and this ‘hit’ is in every single cell of the body. Now, for example, if you are just maintaining the lining of your colon and making some new cells and something goes awry in the remaining good copy of P53 in that cell, it could easily (and most likely will) turn into a colon cancer cell. You see, if the germline P53 mutation wasn’t there, then there would have been functional P53 hanging around to notice that a second new P53 mutation happened and it would have instructed the cell to self-destruct. Unfortunately, that didn’t happen and now this particular colon cell has no functional P53 and it can get out of control pretty fast and make copies of itself unchecked…which is exactly what cancer is.
This second mutation I just discussed where it happens in just one cell is called a somatic mutation. You could have two somatic mutations happen in the same colon cell (this happens), but if you know anything about Vegas, then you know the chances of two hits happening in one cell are way less than just needing one hit because you were born with a bum copy of P53..and this is why some people are at a much higher risk to develop cancer than others…I’ll talk about those tomorrow and how it relates to pediatric cancer.
That got long, sorry, but I hope that makes a little sense! I tried!
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