Cancerous Cell Mutations

From Alex: Gene mutations occur in the body all the time. In order for a cancerous gene mutation to occur the mutation must happen within a stem cell, and effect a gene that is involved with either 1) growth and development or 2) repair of DNA damage.

These classes of genes are referred to as oncogenes and tumour suppressor genes respectively. Specifically, mutations must occur in at least four of these signalling pathways in humans. 

The types of mutations that must occur within growth and development genes are ones that:

  • Affect the control region of the gene and turn it on when it’s supposed to be turned off
  • Cause the gene to stay in its active state longer than its supposed to
  • Last in the body longer than its supposed to
  • Cause it to remain attached to the signaling proteins it affects rather than detaching after its job is done (constitutive signaling). 

How does an oncogene form?
Source: National Cancer Institute

Growth and Development Genes

Normally growth and development genes are only switched on briefly to fix damage to tissue or while you're growing during childhood, otherwise these genes are turned off. However when a mutation occurs and these genes are switched on and stuck in their production phase, called proliferation, these genes are now cancerous and called Oncogenes. 

Tumour Suppressor Genes

The second pair of genes that must mutate, tumour suppressor genes, are genes that fix and recognize DNA damage, also known as ‘checkpoint genes’. These genes are supposed to be switched on all day, every day, for our entire lives. These are the genes that fix DNA damage in all genes and cells. Their job is to recognize when a random amino acids have been added and either fix the damage or stop the cell from reproducing. Mutations can happen in these genes that can:

  • Cause the gene to not be expressed at a high level
  • Damage the binding regions that these genes use to attach to other molecules 
  • Change the genes they interact with, so they turn on oncogenes rather than repair genes

Source: National Cancer Institute

You only need one stem cell niche with alterations to cause a problem.

For cancer to develop mutations must happen in at least four of these pathways in one stem cell niche. Once this has happened we now have unregulated production of mutated cells. 

There are hundreds of documented oncogenes and tumor suppressor genes in our bodies, due to this there are many 1000’s of possible combinations of gene alterations that can lead to cancer. It is not the same for every person and this multitude of mutation possibilities is why the success rates for treatment can vary so greatly from one person to another. Each cancer is unique.

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