ECC 2015
The importance of significant genetic variations between breast cancers
Dr Lucy Yates - Wellcome Trust Sanger Institute and the University of Cambridge, Cambridge, UK
Lucy, you’re from Cambridge, the Sanger Institute, tell me exactly what you’re doing there because your position in the Sanger is what, for instance?
I’ve just finished doing a PhD in the lab of Peter Campbell; I’m a clinician scientist.
Right, so you’re a scientist and a doctor and you’re looking at cancer, you’re looking at relapsed breast cancer. Why were you doing this project looking at the genome and looking for factors to indicate the possibility of relapse?
We know that the very root cause of cancer is defects that develop within the genome of once normal cells. They transform into cancer cells over time as a consequence of these defects in the genome.
Classically we look at the primary, do some tests and say, ‘Ah yes, we can treat it in this way or that way.’ But this might change?
Yes. These findings suggest that even if we see something in the primary tumour that might not necessarily be the same thing later on. We find that often there are additional things have actually happened within the cancer genome over time.
What have you found that has changed?
We have found, by looking at individual cancers, that new cancer genes are sometimes found at relapse that weren’t seen in the primary tumour. We find there’s a wide range of cancer genes that can be involved in that situation. This really gives us a challenge when it comes to precision medicine.
So there is this evolution going on but how can you anticipate that and look for clues so that you could potentially target some of those late changes?
We compared the genomic landscapes of primary and relapsed cancers. We looked at 839 cancers, some of those differences we see suggest that there are certain subgroups of primary cancers that seem to be more likely to relapse. That fits with a lot of previous research looking at gene expression. So that’s one way that we find that potentially if we can isolate that group that would really help us to prevent the relapses at a later stage.
Have you seen any potential therapeutic targets at this stage?
In terms of therapeutic targets we can look at those in the primary tumour or those in the relapsed tumour or those shared by both of them. Actually, the majority of mutations that are targetable are actually present in the primary tumour. So there is hope for targeted therapies at that up-front time. This contrasts to some other cancers where a lot of the events are late that you may target. So actually a lot of the events are in the primary tumour and then the question is these additional events that we see arising late, are they so clinically important we need to be targeting them as well? We will work that out over time by doing more of these sequential sampling approaches.
And you do genome-wide sampling and this could supplement the classical pathological signs.
It’s only going to be by getting big enough numbers that we’re going to be able to break down the complex landscapes we see and start to make sense of them to bring real improvements for individuals in the future.
