DNA doesn’t lie — and exploratory tumor biopsies might soon be a thing of the past
Our body seems stable, but every day, some of our cells die and get replaced. This growth and replacement is necessary for our survival — but sometimes, cell instructions get screwed up to the point that the cell keeps on growing, out of control, dividing and spreading.
This — the unwanted overgrowth of our body’s own cells — is cancer.
And doctors may soon have a new and powerful weapon to spot it, early, without ever needing to find a swollen clump of out-of-control cells. That clump is a tumor, and they take a while to form, which gives cancer more time to spread throughout our body.
Cancer cells’ screwed up overgrowth is a result of mutations in our DNA, mutations that we inherit or pick up over time. That DNA usually stays inside the cells, but not always.
Cells don’t wear pants, but they do have genes
Let’s first talk briefly about DNA.
In an organism, all of the DNA is referred to as a genome, while individual little stretches of DNA are referred to as genes. Each gene is the instructions for how to make a protein, and the genome is a collection of genes + filler DNA. In humans, the genome is spread over 23 different collections, each called a chromosome.
(Analogy time: think of the genome as a book-bound set of cookbooks. Each recipe is a gene, and each book in the set is a chromosome. Each recipe also has some introductory text that talks about where the recipe came from, how it’s served, and other useful tertiary info; that’s the filler DNA that separates genes from each other.)
Only about 1% of the genome is actual genes, which are the DNA that specify the recipe for the proteins that make up the human body. The other 99% is a Wild West of junk sequences, repeated strips that serve as spacers, and other sequences that seem to control whether genes are turned on or off, and how activated they are.
Because most of the DNA in our genome doesn’t actually do anything, we can pick up lots of mutations without dying. This is a feature, not a bug; otherwise, we’d get cancer from our first suntan.
But some areas of the genome remain mission-critical. If a mutation hits these small areas in a cell, it pushes that cell closer to cancer. These areas are classified as either:
- Tumor suppressing genes: these genes, when operating normally, put the brakes on a cell that’s starting to become cancerous. If the tumor suppressor gene is broken by a mutation, it can’t act as a safety brake.
- Oncogenes: these genes can trigger cancerous growth if they get mutated. A mutated oncogene may be stuck in the “on” position, telling a cell to constantly grow.
There are many different combinations or patterns of mutation that cause cancer, but the important lesson is cancer occurs because of mutations in the DNA of a cell.
So… how can we check all our DNA for any cancer-linked mutations, without peering into every cell in our bodies?
DNA from plasma, no Tesla coil required
We can’t look at all our DNA. Remember, each of the trillion+ cells that make up our body has its own full copy of our genome, and mutations don’t affect all our cells equally. One skin cell may have a totally normal, non-mutated copy of our genome, while its neighbor’s DNA has a bunch of dangerous mutations.
We can’t break into every cell; that would definitely kill a person if we popped each cell to look at their DNA, even if we put it back afterwards. But we don’t have to pop all our cells, because they emit DNA into our bloodstream.
It’s not all cells, and it’s not all DNA. But it’s enough to measure — and the levels change when we have cancer.
In all people, DNA ends up in our bloodstream from dying cells, and also from the process by which new red blood cells are constantly formed. (A fascinating side benefit of this is that pregnant women have DNA from their fetus circulating in their blood, which is how doctors test for the sex of the baby, checking if there’s any Y chromosome in the woman’s blood.)
Most of that DNA is from normal cells. It will show some mutations, sure, but not enough in the places that matter to lead to cancer.
But tumors, cancerous cells growing out of control, also dump DNA into our bloodstream. It’s a very low fraction of the total cell-free DNA, but it’s enough for very sensitive sequencing machines to detect.
A recent (September 2023) paper showed that, in a proof of concept model, researchers can spot cancer-causing mutations in the little bits of cell-free DNA extracted from patients’ blood plasma. After training a statistical model, it could predict which patients had Stage IV cancer, even when patients had various different types of cancer (breast, lung, skin, etc.).
Will this replace other forms of cancer testing?
Cell-free DNA holds tantalizing possibility, but there are also limitations. It’s still extremely challenging to tell whether a particular DNA fragment in our blood came from a cancerous cell, or just from a regular cell. Remember, regular cells can (and do) have various mutations, too.
This trial was looking only at patients with advanced cancer, which means more tumor cells pumping mutated DNA into the blood. There will have to be further trials to figure out where the detection limit of cell-free DNA is. How far along does the cancer need to progress before it’s discharged enough DNA to activate the sensors?
A closer approach for cell-free DNA detection might be for monitoring someone’s cancer treatment over time. As cancerous tumors die off from chemotherapy, the amount of cancer-associated DNA in the bloodstream should decrease. This could help doctors monitor the drug’s impact and decide whether to switch to a different prescription.
There’s also still a cost to a cell-free DNA approach. DNA sequencing has gotten far, far cheaper in the last two decades, but it’s still going to cost a few thousand dollars. Additionally, for this study, the researchers had each person’s genome to compare against, making it easier to spot the cancerous mutations.
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Cell-free DNA sequencing may become a monitoring option for people with a high family risk of cancer. Give a yearly blood sample, get the DNA sequenced, and see if any mutations trigger an alarm to go in for a more in-depth cancer screening procedure.
For now, doctor-recommended screenings are still best, especially if you’re at a high risk of certain types of cancer. But one day, the expelled, cell-free DNA floating around in our blood may yield additional insights about our health, and any cancers that might be brewing.
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