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Whole genome sequencing identifies four subtypes of pancreatic cancer

6 March 2015

An international team from Australia and the UK has used ‘whole genome sequencing’ to identify four distinct subtypes of pancreatic cancer. The findings could help improve existing treatments for patients by matching therapies that suit individual patients’ type of tumour best.

The study, published in the prestigious journal Nature, reports an in-depth analysis of 100 pancreatic cancer genomes. The findings reveals broad patterns of variation that have been classed as ‘stable’, ‘locally rearranged’, ‘scattered’ and ‘unstable’.

The genome is the entire set of instructions needed for creating an individual person. Millions of individual instructions are contained within DNA molecules and groups of DNA – genes – contain the instructions for making proteins, which carry out essential functions in the body.

Whole genome sequencing is like satellite imaging – it allows us to look at both the whole landscape and zoom in on specific areas to see where DNA codes have changed, or mutated. Mutations can happen for many reasons, including mistakes in copying DNA when cells divide, and the results of this can create new versions of genes or cause genes to switch on or off at the wrong time.

The researchers studied the ‘structural variation’ of the DNA shuffling, and categorised the changes into the four broad types of pancreatic cancer.

The study was led by Professors Andrew Biankin and Sean Grimmond, based at the Wolfson Wohl Cancer Research Centre, part of the University of Glasgow, together with Dr Nicola Waddell from the University of Queensland's Institute for Molecular Bioscience, who interpreted the sequencing results.

Professor Biankin said: “Many different kinds of catastrophic event can happen in a cancer genome. They can be described broadly… like geographical events—such as ‘volcano’, ‘earthquake’ or ‘storm’. You will never witness two identical volcanoes, or two identical earthquakes—but there is enough similarity to group them.

“Doing whole genome sequencing gave us a much clearer picture than we had before. We were able to reflect our analysis onto the patients, and started to see better association between readouts, therapies, and outcomes. The bottom line is that we really have to start thinking about moving to whole genome sequencing as a diagnostic imperative.”

The group hopes that this would allow treatments to be selected for individual patients based on the type of tumour identified through whole genome sequencing.  Already, for example, the study suggests that patients with ‘unstable’ genomes may respond well to platinum-based drugs, which damage DNA or, potentially, to drugs which prevent cells from repairing DNA.

Biankin plans to conduct a clinical trial in the UK for patients with pancreatic cancer which could be useful in a number of ways:   

“So for example, if we’re using a novel immunotherapy, and we don’t yet have a biomarker, we’ll give it to all patients, and we’ll test their genomes to see which ones respond and which don’t.

“We’ll also have the various genome subtypes that have come out of this study—where in some cases we can see that mutation corresponds to a particular drug target. We’ll select those patient groups and test the targeted therapy we believe should work,” he said.

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