DNA - Cancer Research UK - Science Update blog

Watching cancers evolve using ‘liquid biopsies’

Posted on April 8, 2013 by Henry Scowcroft

Cancer’s evolving DNA can be detected using a blood test

Sometimes it feels like cancer research is progressing at a dizzying speed.

Just last year, we reported how Cancer Research UK scientists had reconstructed the evolution of a patient’s kidney tumour during treatment – one of many studies over the past few years illustrating cancer’s fearsome genetic complexity and adaptability.

This phenomenon, known as ‘intratumour heterogeneity’, led many to predict a long, hard slog to fully understand it – let alone get a handle on its implications for treatment.

One key concern was that patients would need to undergo a series of small operations (biopsies) to take repeated tissue samples to track how their cancer develops – and that this could be painful, costly and risky – especially for cancers deep in the body. And even then, because of the genetic variation within each patient’s cancer, there would be no guarantee that the biopsy results would represent an accurate picture.

Others also pointed out that such heterogeneity was a blow to the optimism around new-generation ‘targeted’ therapies, designed to treat cancer cells driven by individual mutations.

But recent discoveries have renewed this optimism. It turns out that tumours release DNA into the bloodstream, and that this seems to contain signals about what’s going on inside it. Consequently, there’s been a growing hope that analysing these DNA fingerprints could provide a quick, simple ‘liquid biopsy’ to track tumours’ progress.

And last month, researchers at our Cambridge Institute published compelling evidence that circulating DNA could indeed be used to take a snapshot of the DNA errors (mutations) in a patient’s breast cancer.

Today they’ve gone one step further proving, in a beautifully detailed paper in the journal Nature, that blood samples can be used to monitor genetic changes in a patient’s disease over time.

This has the potential to be a game-changer, and rapidly accelerate research into what makes cancers tick, in real patients, in timeframes that can impact on clinical decision making.

Let’s look at what they found.

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Gene variations and cancer risk – more results, more answers and more questions

Posted on March 27, 2013 by Kat Arney

Scientists have found around eighty new gene variations linked to breast, prostate and ovarian cancers

A thousand scientists from one hundred international research groups working over four years. Thirteen papers spread across five journals. DNA analysis of two hundred thousand people. And eighty new genetic variations, or SNPs (pronounced “snips”) linked to three different types of cancer, doubling the current total known about so far.

These are impressive, big figures from an equally impressive, big piece of science, which Cancer Research UK helped to fund (here’s the press release). But what does it all mean?

To find out, we spoke to Professor Doug Easton from the University of Cambridge, one of the leaders of the project.

Cancer Research UK: What exactly are SNPs?

Prof Easton: SNP stands for “single nucleotide polymorphism”, and it’s a single ‘letter’ difference in the DNA between individuals. Your DNA is made up of around 3 billion of these ‘letters’ – there are four possible letters you can have: A, C, T and G – so a SNP is just a single place in your genome where you might have one particular letter, and someone else has a different one.

To explain a bit more about SNPs and what they do, have a look at this short animation:

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Blood test tracks breast cancer

Posted on March 13, 2013 by Kat Arney

A blood test could provide a simple way to monitor cancer

Cancer is a wily enemy. It mutates and spreads within the body and becomes resistant to treatment. Understanding and counteracting this tricksy behaviour is the greatest challenge for researchers and doctors, and is the key to bringing forward lasting cancer cures.

Thanks to advances in technology, we’re now starting to map out cancer’s underlying genetic landscape. In theory, if doctors knew exactly which gene faults were driving a patient’s cancer, they could give them the most appropriate targeted treatment.

And as well as selecting the therapy with the best chances of working, it’s also important to know whether the disease is responding to treatment or not as fast as possible, so doctors can decide on the best course of action – for example, whether to continue with a particular drug or switch to a different one.

But there’s a problem with this approach. Monitoring how well a patient’s cancer is responding is not a simple job. At a minimum, it requires regular scans or other tests. On top of this, analysing a tumour’s genes requires having a sample of it, usually taken as a biopsy with surgery, as well as access to tests that can provide meaningful results in a short timeframe. And if the cancer has spread to a multitude of locations in the body, it’s simply not possible to biopsy them all.

As an extra kicker, we now know that a single tumour can house cancer cells with a range of different gene faults – a characteristic that scientists refer to as “intra-tumoural heterogeneity”, but could also be described in rather more unpublishable words. And secondary cancers that have sprung up elsewhere in the body also have differences in their genetic makeup compared to the initial tumour.

The problems seem almost insurmountable – it’s a bit like trying to attack a shape-shifting army that we can’t properly see. But, as you might hope, research is coming to the rescue.

Building on work we talked about last year, scientists at our Cambridge Institute have made a significant step forward in developing a relatively simple genetic blood test that can monitor breast cancer as it progresses.

They’ve published their results in a paper in the New England Journal of Medicine, and although the title – “Analysis of circulating tumor DNA to monitor metastatic breast cancer” – may not set your heart racing, the contents are certainly inspiring for all of us hoping for progress in cancer research.
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Order from chaos – making sense of bowel cancer’s scrambled DNA

Posted on February 27, 2013 by Henry Scowcroft

Unstable chromosomes can make bowel cancer worse

Last year, researchers at our London Research Institute published what became – after the discovery of the Higgs boson – the second most-referenced science paper of 2012

Their study looked at how tumours ‘evolve’ during treatment, and showed that, genetically speaking, different parts of a patient’s kidney tumour were extremely diverse. No two regions they analysed were identical.

Although not the first study to demonstrate this diversity – known as ‘intratumoral heterogeneity’ – this paper kick-started a wider discussion of its causes and implications. Understanding how diversity develops in a tumour is important – because this is how cancers develop resistance to chemotherapy, and ultimately what makes cancer such a killer.

Today, the same group has published new research in the journal Nature that starts to reveal diversity’s origins.

They’ve been studying a phenomenon called ‘chromosomal instability’ in bowel cancer cells, where cells’ DNA becomes more and more disordered as they grow and divide, causing ever-greater genetic chaos. Patients with more unstable tumours tend to do worse - so understanding how it develops is important.

In a series of meticulous and detailed experiments, the researchers have found compelling evidence that chromosomal instability is caused by the malfunctioning of a particular (and unexpected) step in cell division, and identified three genes involved.

This gives us a better understanding of instability’s causes, which hopefully will galvanise future work to exploit it, and ultimately to improve things for patients. Let’s look in detail at what they did.

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Notes from the NCRI conference (day 3)

Posted on November 6, 2012 by Henry Scowcroft

It was another day of fascinating talks

It’s been another packed day at the NCRI conference, full of interesting discussion and debate (as were yesterday’s and Sunday’s sessions).

But before we get stuck into the day’s events, it’s worth flagging the overnight media coverage from the meeting, with OnMedica covering this story on prostate screening, while the BBC was one of several news outlets to cover a promising potential method to detect cancer.

And now to the main event.

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Twenty-five years since landmark bowel cancer discovery

Posted on August 28, 2012 by Josephine Querido

Professor Sir Walter Bodmer who helped locate the APC gene 25 years ago.

There’s a lot more to do before we can say we’ve beaten cancer, but every now and then, it’s good to sit back and reflect on how far we’ve already come.

Back in June, when the country was celebrating the Diamond Jubilee, we took time to think about how much cancer research has changed since the Queen came to the throne.

And this month, we’re proud to look back at one of our key achievements, which has played a big role in the lives of the one in twenty patients who’s bowel cancer is inherited.

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Melanoma genome reveals UV damage and treatment targets

Posted on August 22, 2012 by Kat Arney

Researchers have finally pinned down the link between UV radiation and gene faults that drive melanoma. Image source: Wikimedia Commons

We all need a bit of sunshine in our lives – something that’s often lacking in the Great British Summer.

But while UV light (radiation) from the sun helps our bodies to make vitamin D, which is vital for building healthy bones, there’s a dark side to UV. It damages our DNA – the genetic ‘instruction manual’ in all our cells – which increases the risk of skin cancer.

Researchers have shown that eight out of 10 cases of malignant melanoma – the most dangerous form of skin cancer – are caused by getting too much UV, either from the sun or sunbeds. There’s also good evidence from population studies to show that getting sunburned at any age doubles the risk of developing melanoma later in life, and people who have the highest levels of UV exposure also have a higher skin cancer risk.

But up until now, there’s been an inconvenient problem for researchers studying precisely how UV-induced DNA damage leads to skin cancer: the major gene faults known to be involved in melanoma don’t actually show the hallmarks of UV damage. And because UV can cause such widespread damage throughout our genome, it’s been hard to pin down exactly which other genes might be involved in the disease.

Thanks to the advent of high-tech genome sequencing technology, this conundrum may have now been solved by two research teams in the US. Their results prove beyond doubt that UV-induced genetic damage can drive the development of melanoma, and highlight important new targets for future treatments for the disease.

Let’s take a closer look at what they found.