The Cancer Genome Atlas - The value of dna sequencing

[MUSIC] GIBBS: DNA Sequencing is a process where we determine and identify every single DNA base, every single DNA element that is in the genome of an individual. There are six billion of those in every normal cell in every person. When we apply DNA sequencing in the cancer project, we first figure out what those six billion DNA bases are in the normal cells in that person, and then we take some of the tumor in that person and figure out what the DNA bases are in the tumor. CHIN: In a cancer, the DNA’s change in many ways. If you think of your DNA sequences as a book, the way you can change is that you can lose a whole paragraph of it like a deletion, or you can duplicate a paragraph or a page multiple times. Or you can have a misspelling, a single letter that’s been changed or pieces that go into the wrong place. The pages fall apart and you put it back together in the wrong order. Any of those disruptions will lead to misread when the cells proliferate and leads to mistakes and altered behavior in the cell. When you have enough of those things go wrong, you become cancerous. GABRIEL: In a typical genome, we might see thirty sites that differ between a persons normal genome and their tumor genome, but we look very closely at these thirty differences to try to figure out which ones are the meaningful ones and one way we do that is to look across many peoples tumors. We say, “is this gene hit very often?” We have to use DNA sequencing at large scale for this type of project, because the point here is to really do a systematic survey across many genomes. We can look at a small number of samples and be able to make guesses and say, “well this one might be a recurrent change, this one might be important.” To get down to the rare events which might lead us to new areas of therapeutics or new understandings of why a tumor arises, we have to be able to find events that occur only at a three percent level or a five percent level and unless you’re studying hundreds of samples, you’re never going to find those events. You just simply don’t have the statistical power to find them. SPELLMAN: We’re looking forward to the thousand dollar genome or the hundred dollar genome so that we can do these analyses on tens of thousands of samples and we can follow tumors not just once, but look at the DNA sequence of the tumor as it responds to therapy and look to see how it’s changing and we can adapt our therapeutic regimens as the tumor evolves. GIBBS: Sequence information is going to be used at all different levels. So, there will be some who will just use the very endpoint of this project, which is the knowledge of which particular genes can be important in which particular cancer. That can spawn a whole career of research into the mechanism of what’s going on in that cancer. Others will want to look at every single base in a particular disease, every single DNA letter in that particular disease that they’re studying because they’ll want to know all of the subtleties that can occur under all of the different circumstances in that disease. So, there’s a generality of how things will be used, but there’s one thing that will be common to everybody who’s either studying cancer or treating cancer and that is that they will have to become versant in the language of DNA. [MUSIC]