Sanger Institute - What is Kataegis?

Uploaded by sangerinstitute on 18.05.2012

Kataegis is a phenomenon that we have found in breast cancers
And it's characterised by localised hypermutation
Or a large number of mutations very closely clustered together
Now cancers have many, many thousands of mutations
And we would expect that these mutations would be dispersed pretty much randomly through the genome
The genome of course is three thousand million bases
So even for a cancer that has three thousand mutations
You'd still only expect most mutations to be every million bases or so
And that's what we see in this plot, which we call a rainfall plot
The dots represent individual mutations and the different colours are the different mutation types
We expect most mutations to be clustered around a million base pairs
What we have found in the breast cancers is that we find clusters of mutations
That have much shorter inter-mutation distances, much shorter distances between mutations
And that they can be distributed throughout the cancer genome
Another point to make here is that the colours of the dots are very particular
In this genome you have a lot of red dots, or C to T mutations
The black dots which are C to G mutations
But they are distributed through many, many chromosomes in the genome
This is a very particular cancer which has a very dense cluster of mutations
That is just situated on chromosome six
But these mutations are almost entirely C to T mutations
Because of the nature of these mutation showers we have called it Kataegis
Which is Greek for showers or thunderstorm because it looks like a mutational thunderstorm
But this localised hypermutation had a few interesting characteristics
They were characterised by very particular mutation types
And there were cytosine changes thymine, cytosine changes to guanine
But they also happened at a particular sequence context
So the cytosine's were almost always preceded by a thymine, TpC context we call it
Furthermore, these substitutions were co-localising with another type of mutation which we call rearrangements
And this is a phenomenon that's never been seen before
And we could not have hoped to see it before we could look at the entire muation catalogue in these cancer genomes