How the landscape of the pancreatic cancer genome is coming into view

IMAGE:This is professor Andrew Biankin. view more

Credit: Garvan Institute of Medical Research

Scientists from Australia and the UK have done the most in-depth analysis yet of 100 pancreatic cancer genomes and highlighted 4 subtypes that may help guide future patient treatment. The study is published in Nature today.

Using whole genome sequencing, the team revealed broad patterns of 'structural variation', or change, previously invisible when it was feasible to sequence only protein-coding genes (around 1% of the genome).

Just as satellite images allow us to see the Earth as a whole, and zoom into the detail when we choose, whole genome sequencing allows us to view global and local DNA damage equally effectively.

Like landmasses or ice shelves, entire chromosomes can shatter and rearrange themselves. Slabs of DNA can break away from one chromosome and join another. Genes can be inverted, deleted or multiplied.

With the benefit of a global view, four kinds of genomic rearrangement were detected in the new study, including 'stable', 'locally rearranged', 'scattered' and 'unstable'. In some cases - notably 'unstable' genomes, which show defective DNA repair mechanisms - effective treatments suggested themselves.

Professors Andrew Biankin and Sean Grimmond, laboratory heads at Sydney's Garvan Institute of Medical Research and the University of Queensland's Institute for Molecular Bioscience (IMB) respectively, led the study, arising out of a much larger ongoing project. Both are now based at the Wolfson Wohl Cancer Research Centre, part of the University of Glasgow in Scotland. They collaborated with bioinformatician Dr Nicola Waddell from IMB, who interpreted the sequencing results.

A prior study by the same group, which examined only the 'exomes' - protein-coding genes - within the same cohort of 100 patients, showed a complex mutational landscape, as well as enormous heterogeneity among the tumours. Thousands of mutated genes were present, and "a long tail of infrequently mutated genes dominated", said Professor Biankin.

"The bottom line is that we really have to start thinking about moving to whole genome sequencing as a diagnostic imperative.

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How the landscape of the pancreatic cancer genome is coming into view