New genetic links to pancreatic cancer discovered

Researchers have used whole-genome sequencing to uncover new mutations responsible for a rare type of pancreatic cancer.

Nearly all patients with pancreatic neuroendocrine tumours (PanNETs) studied had no family history of disease, but the scientists found a clear genetic predisposition. They were also able to link PanNETs to genes associated with other cancers.

'In the future, patients at risk of this rare pancreatic cancer could be identifiable through genetic screening,' said the study co-leader Dr Nicola Waddell, QIMR Berghofer, Australia. There is currently no reliable test for pancreatic cancer.

Pancreatic cancer affects 1 in 71 people. The Australian team studied 102 patients diagnosed with PanNETs, which account for five percent of pancreatic tumours. The symptoms of PanNETs can be difficult to detect and diagnosis is often in the late stages; mortality rates are 60 percent.

The researchers looked for genetic mutations in tumour cells and also in somatic cells of the body that reveal germline mutations, which are heritable. Previously it was thought only five percent of PanNET tumours were linked to heritable genes, but the researchers found that a surprisingly high proportion of the mutations (17 percent) were linked to germline mutations. Mutations were associated with genes involved in DNA repair, cell proliferation, cell survival and cell ageing; processes almost universally disrupted in cancer.

The researchers were also surprised to find PanNETs could be linked to gene mutations known to predispose individuals to other cancers.

Professor Sean Grimmond of the University of Melbourne, co-leader of the study, said: 'We found that the MUTYH and BRCA2 gene mutations, normally associated with colon and breast cancers, also appear to play an important role in PanNETs… This raises exciting possibilities for how we treat this disease in the future.'

PanNETS are highly unpredictable and determining the appropriate treatment is a challenge. The researchers say that exploring the 'genomic landscape' of PanNETs, could help clinicians decide on the best therapy for an individual, potentially saving patients from unnecessary, aggressive treatments. The findings could also be used to identify people at risk of these cancers.

The patients were recruited via the International Cancer Genome Consortium, and the Australian team collaborated with researchers from the US and Europe. Professor Andrew Biankin, director of translational research at the University of Glasgow and co-lead of the study, said: 'This study is a great example of International Team Science… We managed to overcome all the societal hurdles of data and material sharing to make significant findings in an uncommon cancer type that can be difficult to treat.'

The study was published in the journal Nature.