Breast Cancer: A Deeper Understanding

Uploaded by sangerinstitute on 17.05.2012

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