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These are all good questions, and full disclosure I know only the basics in this area. DNA can be identified as cancerous for a variety of reasons, though typic
by entee 9y ago
These are all good questions, and full disclosure I know only the basics in this area. DNA can be identified as cancerous for a variety of reasons, though typically what you're looking for is some mutation you know to exist in cancer. This could be a single point mutation (insertion/deletion/change of a given DNA base pair), a loss/gain/modification of several adjacent base pairs, or whole scale genome rearrangements (deletion, insertion, inversion, replication) that will result in of two pieces of DNA being adjacent although you know they shouldn't be next to one another (see https://en.wikipedia.org/wiki/Philadelphia_chromosome https://en.wikipedia.org/wiki/Philadelphia_chromosome for a quite well known example). You could also look for copy number variation (gene X has way more or way fewer copies than expected). I'm probably missing some as well, but those are the biggies.
To detect these, you're going to use either something like microarrays, QPCR, or DNA sequencing. Today people talk almost exclusively about high-throughput sequencing (HTS) because it has gotten quite cheap, gives you large amounts of data, can be made massively parallel and isn't as hindered by needing to know very precisely what you're looking for (microarrays and QPCR require somewhat more targeting; HTS also needs you to know what you're looking for, but not in quite the same ways).
In all of those cases you need a sample of DNA (duh). These can all be made to work if you have a single cell in hand, it's tricky but sample prep does exist for single cells at a time. Trouble is, you need that cell in hand. There are about 5L of blood in the human body. A human cell will range from 1-10 pico-liters. You will take a blood sample of 2 milli-liters. Chances are pretty slim your one cell will be in that 2mL. Even if it is, there are billions of other cells in that 2mL adding additional noise. Usually though, we're looking at circulating DNA fragments with these technologies, and depending on the stage of the cancer and the type of cancer, there may be enough to pick up on in the blood. How to do that best is an area of active R&D.
Just dug up review if you want to learn more:
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002205 http://journals.plos.org/plosmedicine/article?id=10.1371/jou...
- jacquesm 9y ago> Even if it is, there are billions of other cells in that 2mL adding additional noise. Billions? I think you meant millions.
- sillysaurus3 9y agoThank you very much for the breakdown and the reference! For some reason I assumed that this detector would be embedded into your circulatory system, so that it eventually scans all 5L of blood in your body rather than getting lucky with a 2mL draw. Now that I say it, it sounds pretty unrealistic, but I wonder if it's even remotely possible.
- entee 9y agoSo if we want to get a little sci-fi but still within the realm of not-physically impossible... If you wanted to monitor for a very specific piece of DNA or a small number thereof, you could have an inline piece of hardware that samples the blood continuously, trying to enrich for those. You could then use a hybridization-based (kinda like a microarray) test to check for the presence of that DNA. Right now, the relevant technology just isn't there. You'd need new materials (of the top of my head they'd need to be highly resistant to fouling, among many other properties), probably a completely new filtering/enrichment system (again fouling and clogging and specificity and sensitivity are huge problems here), and a decent, cheap, high sensitivity and reliability hybridization based detector. All of those things are quite hard, but I don't think they're completely impossible. I do think it's highly unlikely we'll be seeing this in the next 5-10 years though. But I could be wrong! :)
- kanzure 9y agoA similar device was proposed a while back-- a nanopore DNA sequencing array implanted into the heart that checks all circulating DNA. In context, the authors had proposed embedding some enzymes in every neuron to record action potentials, neurons would excrete the DNA into the bloodstream, and then you would recover the entire connectome and all the action potential history by DNA sequencing any circulating DNA that makes it to the heart.
- deleted 9y ago[deleted]