Prof Charlie Swanton, Cancer Research UK London Research Institute
Kat - Moving from mice to humans, this month the charity Cancer Research UK announced their own ambitious project, sequencing the genes in tumour samples from more than 800 patients with lung cancer and tracking how they evolve over time in response to treatment. It’s hoped that the study, called TRACERx, will revolutionise scientists’ understanding of the genetic faults that underpin lung cancer, and reveal more about tumour evolution and so-called “tumour heterogeneity” - the fact that cancer cells within a single patient can have different genetic makeups. Here’s the project’s leader, Professor Charlie Swanton, talking to Cancer Research UK’s Greg Jones.
Charlie - So, we’re going to be looking at how lung cancers, principally non-small cell lung cancers change over time and how their spatial and temporal variation gives us some insights into potential new therapeutic strategies for patients. So, what we’ve realised from our work over the last year or two is that tumours are not just single entities but they're composed of multiple different subclones that maybe intermingled or spatially separated. What we’re also realising that tumours are evolving over time. So, there’s a spatial and temporal aspect of tumour biology that many of the sequencing approaches we’ve been taking so far have largely not taken into account. Principally because of the cost involved and also, I think the awareness now that tumours are markedly more heterogeneous than perhaps we had imagined initially.
So, the idea with TRACERx, which stands for Tracking Cancer Evolution Through Therapy, is that we ask patients with primary non-small cell lung cancer to consent this study which would enable us to acquire any tumour material that is surplus to pathology requirements, following surgery - so, these are patients with primary operable lung cancer - and then we will subject each tumour to multiple sequencing approaches to identify what are the shared mutations in every region and what are the diverse heterogeneous mutations in every region.
If the patient is unfortunate enough to suffer recurrence of disease or metastatic disease, we’ll ask if the patient would kindly consent to a further biopsy so that we can then compare the biopsy sites to of metastatic disease. So, the original primary to ask the principal question, how has the disease changed over time, to better understand the biology of metastatic disease, to better understand resistance to therapy, and ultimately, to come up with better clinical approaches to treat this disease to stop this from happening.
Greg - Can you explain why this is going to be such an enormous undertaking in terms of the amount of data you're going to generate?
Charlie - So, we’re sequencing tumours from 850 patients, but we’re not sequencing just one tumour. We’re sequencing up to 6, 7, or even 8 coding exomes from each tumour during the disease course. Now, a coding exome has about 50 million base pairs and we’re sequencing at a depth that is relatively unprecedented in these studies - at 500 so-called X coverage. And so, if you take that into account, along with the number of tumours we’re sequencing in a number of regions we’re sequencing within each tumour and comparing primary to metastatic states, we’re talking a need or requirement of probably 6 petabytes worth of data storage. That’s the equivalent of probably sequencing 42,500 whole genomes at one X coverage in order to really get to grips with the diversity within a single tumour.
Kat - That was Professor Charlie Swanton from the Cancer Research UK London Institute.