Breast Cancer: A Deeper Understanding – Sanger Institute

Breast Cancer: A Deeper Understanding – Sanger Institute


In these two studies we set out to analyse the entire genomic sequence of human breast cancers In the past cancer research has always focused on identifying individual cancer genes Because these become targets for cancer treatments But a cancer has many thousands of mutations, not one, five, or ten And what we wanted to do was use the full breadth of these mutations To try and see whether we could understand a little more about the development of the cancers I think that these studies show that cancer is incredibly complicated Far more complicated than we’d like it to be We kind of imagined going into it that actually each breast cancer would look pretty similar to every other breast cancer But in fact there are at least seven or eight different processes that are causing mutations And they operate to different degrees in different people We can also tell the timing of these processes We can tell which ones have come on early, which ones have come on later So we can see additional structure in the development of cancers And it’s far more complex than we’d ever thought A little bit like being an archaeologist, we can look back and follow the onset Of these mutational processes when they develop, how many mutations they contribute How they change the genetic landscape, if you’d like, of the tumour And that gives us a really powerful way into correlating this with the way the cancer’s developed Potentially it’s clinical outcome, how it responds to treatment and so on We found multiple mutational processes, some of which are known and others which are novel In particular we found a process called ‘kataegis’ Which is characterised by localised hypermutations, so lots and lots of mutations In a very small region in the genome And this is a phenomenon that has never been seen before and we could not have hoped to see it Before we could look at the entire mutation catalogue in these cancer genomes We now must explore much more exhaustively the world of cancers For the presence of these mutational processes Thus far we have sequenced 21 whole breast cancer genomes But now here and in other places around the world there is going to be sequencing of thousands and then tens of thousands of cancer genomes And from those, we are going to be able, I’m sure, to see evidence of the activity of a number of other mutational processes and indeed these ones too That’ll give us a much more complete idea of what has been causing the mutations in our cancers In other words what’s been causing our cancers in the first place

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