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Home | News | Landscape of pancreatic neuroendocrine cancer

Landscape of pancreatic neuroendocrine cancer

Published: 15th February 2017

The whole-genome landscape of pancreatic neuroendocrine tumours is published in Nature today.

The research, which was led by the ARC-Net Research Centre of the University Hospital of Verona, Italy, with significant contributions from the University of Glasgow and the Australian Pancreatic Genome Initiative, examined a number of neuroendocrine tumours (NETs), specifically those which are found in the pancreas (PanNETs), the most common form of this rare cancer.

NETs are relatively rare and represent less than 0.5% of all malignant tumours. The most common NETs are those that arise in the gastro-entro-pancreatic tract (70%), followed by those affecting the lungs (20%) and other body parts such as skin, thyroid, parathyroid and adrenal glands (10%). They are low-incidence tumours, but with high prevalence, often because patients live for many years with the disease. However, these tumours can also be fatal – for example, Apple co-founder Steve Jobs died of a pancreatic neuroendocrine tumour after having the disease for several years.

It was discovered that we may inherit more than twice the number of ‘cancer genes’ than experts previously thought. Researchers found that there were a significant number of inherited mutations in this type of cancer – 17% of PanNETs cases investigated were linked to inherited faulty genes. Previously it was thought only 5% of tumours were linked to hereditary genes.

Using international expertise the study also discovered how mutations affected different genes and their functions. Four key cellular processes were affected by mutating genes including: the DNA repair systems, the systems that control cell growth, the systems that regulate the processes of cellular raging and the systems that regulate chromosomal structure. The study was coordinated by the Veronese multicentre team of Arc-Net, led by Professor Aldo Scarpa, which brought together pancreatic cancer expertise from around the world.

Professor Scarpa said: “In this study we studied 160 PanNETs. By sequencing the genome of these tumours we have decrypted the landscape of genetic alterations of these tumours. This discovery will allow us to target the development of specific therapies that aim to counter the alterations identified.”

Professor Andrew Biankin, the University of Glasgow’s Regius Chair of Surgery and the Director the Wolfson Wohl Cancer Research Centre, said: “One of the most provocative findings is that these cancers had a larger than expected inherited gene defect that likely contributed to their development, potentially raising challenges in the clinic and refocusing future studies in the area.”

This particular study is a great example of International Team Science achieved under the auspices of the International Cancer Genome Consortium. 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. Glasgow is proud to make a substantial contribution to this project led by Aldo Scarpa in Verona, Italy along with our Australian colleagues at the Australian Pancreatic Genome Initiative.”

Dr David Chang, one of the first authors on the paper, said: “This is the largest and most comprehensive study to date on pancreatic neuroendocrine tumour – a relatively rare pancreatic tumour type – using next generation-sequencing technology. We now have a deeper understanding of the molecular pathology of PanNET, including defining specific ways which these tumours can mutate. Importantly, we identified key biomarkers in tumours that could lead to better treatment options.”

Leanne Reynolds, Head of Research at Pancreatic Cancer UK, said: “This promising research could lead to every patient with a PanNET tumour receiving the right treatment at the right time, which could give them the chance to live for longer. While there are existing treatments for PanNETs, we can’t currently predict which treatment would be most effective for each patient, but these new insights could change that in the future.

“We must now invest in further research to develop tests to show us the sub-type of PanNET tumour each patient has, which could then allow them to be fast tracked to the best treatment for them. Because 80 per cent of pancreatic cancer patients are diagnosed at an advanced stage, matching patients with the most effective treatment as quickly as possible is absolutely vital. That’s why we will be funding research into this area as part of our new five-year research strategy, which we launched today.”

AOUI Verona is a national and international reference for pancreatic diseases. Verona, thanks to the applied Arc-Net Research Centre, represents Italy in the International Cancer Genome Consortium (ICGC) with the support of the Ministry of ‘Education, Universities and Research and relevant contributions from the Ministry of Health and AIRC, Italian Cancer Research Association.

The study was funded by the Italian Ministry of Research; Associazione Italiana Ricerca Cancro, Fondazione Italiana Malattie Pancreas – Ministero Salute, Wellcome Trust, Cancer Research UK, Pancreatic Cancer UK, The Howat Foundation; University of Glasgow; National Health and Medical Research Council of Australia, Australian Cancer Research Foundation; Cancer Council NSW; Cancer Institute NSW.

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