Breakthrough research into pancreatic cancer gene mutations

A large-scale international study into pancreatic cancer has discovered that the cancer is not just one disease, but many.

Pancreatic cancer is the fourth leading cause of cancer death. It has the highest mortality rate of all major cancers, with less than one in 20 of those diagnosed remaining alive after five years, and is one of the few for which survival has not improved substantially over the past 40 years.

The study ‘Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes’, published in the journal Nature, represents the first report from Australia’s contribution to the International Cancer Genome Consortium (ICGC), which brings together the world’s leading scientists to identify the genetic drivers behind 50 different cancer types. It presents the collective findings of a research network consisting of the Australian Pancreatic Cancer Genome Initiative (APGI), the Baylor College of Medicine Cancer Genome Project and the Ontario Institute for Cancer Research Pancreatic Cancer Genome Study.

Professor Sean Grimmond, from the Institute for Molecular Bioscience (IMB) at the University of Queensland, and Professor Andrew Biankin, from The Kinghorn Cancer Centre at Sydney’s Garvan Institute of Medical Research/St Vincent’s Hospital, led an international team of more than 100 researchers that sequenced the genomes of 100 pancreatic tumours and compared them to normal tissue to determine the genetic changes that lead to pancreatic cancer.

Professor Grimmond said the study found over 2000 mutated genes in total, ranging from the KRAS gene, which was mutated in about 90% of samples, to hundreds of gene mutations that were only present in 1 or 2% of tumours.

“So while tumours may look very similar under the microscope, genetic analysis reveals as many variations in each tumour as there are patients,” Professor Grimmond said.

“This demonstrates that so-called ‘pancreatic cancer’ is not one disease, but many, and suggests that people who seemingly have the same cancer might need to be treated quite differently.”

The study also revealed two completely new areas where mutations had not been suspected before. These were in chromatin remodelling (modification of DNA and proteins in the nucleus of a cell) and in axon guidance (the process by which neurons send out nerve fibres).

“Identification of these pathways may lead to new drug discovery programs we can use to inhibit the spread of pancreatic cancers,” said UWA researcher Adjunct Associate Professor Nik Zeps, who coordinated patient contributions to the project in WA.

The University of Newcastle’s Dr Chris Scarlett, who is affiliated with the Garvan Institute, said it was rewarding to be involved in a landmark cancer discovery.

“This is the largest collaborative pancreatic cancer study ever undertaken and this finding will have a massive impact on the way pancreatic cancer patients are treated,” he said.

The research group said individual genetic diagnoses and treatments are the future of healthcare.