Question: How do you find the mutations in your work? Do you need to know all the basis in a geno?

Ken Dutton-Regester answered on 16 Mar 2012:

Yeah you are on the money- the reason we have made so much ground and have had success in understanding cancer in the last decade is because we completed the Human Genome Project. This was a large project started in the 90s that scientists all around the world came together to sequence the first human genome- that is, the entire sequence of your DNA from start to finish (about 3 biillion bases). This project was completed in 2000 (that was a draft, the full version was completed in 2003). With its completion came a whole new wave of technology- some is discussed on my profile- that has allowed us to sequence genomes quicker and cheaper.

How we go about finding mutations is that we first sequence a tumour to identify all the mutations or DNA variations in it. In this process- the sequencing data we collect is aligned to, or compared against, the complete version of the human genome that was completed in the Human Genome Project (In a sense, this genome is considered a bible or reference point for all future research). When we align both sets of data you can identify changes in the tumour that are different to the Human Genome Project Genome. Because the genome is so big, we have crazy computers and algorithems that do all the work for us. It then gives us a big read out of all the variations or mutations that the tumour has.

Interesting fact- the seqeunce of the Human Genome Project is actually made up of the DNA of a bunch of people (maybe 8 or so, not sure on the exact number) and not just a single person. This is an important point. There is actually a lot of variation in DNA between individuals. This can include differences in single bases or letters in our DNA, these are known as ‘single nucleotide polymorphisms’ (or SNPs). These SNPs are one of the variations that make us individuals, why we look different, and why we have different risks for developing different diseases. Some of these SNPs are very common across poeple (ex. 50% of people might have a C at one SNP while another 50% will have a G); others are rare or specific to the individual (ex- only 1% of people will have a C while 99% will have a G).

All of this is important as when we sequence a tumour, some of the variations or mutations that might pop up in our list may actually be one of these SNPs and is present in that individuals DNA (these SNPs are not considered to cause the cancer although in reality- some might contribute to the development of the cancer). For this reason, when we sequence a tumour, we also need to sequence the normal DNA of the individual (usually taken from the blood). What we do then, is overlap the variations or mutations between both lists to find the mutations that only occur in the tumour sample. These are the mutations we are interested in as these are the ones that contribute to the development of the cancer and what we might be able to develop new drugs against.

Wow, that was a big story!