An international team of researchers has discovered that an altered version of a gene called Palladin causes an inherited form of pancreatic cancer. The findings, published online in the journal PloS Medicine, also reveal that the same gene is involved in sporadic cases of the disease. The Palladin gene makes a protein involved in forming the cytoskeleton, which gives cells their structure. The mutated form makes cells able to move more easily than usual, allowing them to invade surrounding tissue, say the scientists.
Most cases of pancreatic cancer are not inherited, but around ten per cent are thought to be caused by a mutated gene. The disease is one of the most aggressive forms of cancer - most patients die within a year of being diagnosed, while 95 per cent die within five years. In the UK, there are over 7,100 cases of pancreatic cancer and 7000 deaths each year.
The discovery that the Palladin gene is involved in pancreatic cancer marks the end of a ten year search by co-author Dr Teri Brentnall, of the University of Washington. One of her patients described the illness as his family's 'curse', as it had caused the deaths of his grandfather, father, four uncles and three cousins.
Dr Brentnall carried out detailed studies on the family, comparing DNA samples from those with pre-cancerous cells to those who did not have the disease. The work eventually pointed to an area of chromosome four, containing many different genes. Researchers based at the University of Pittsburgh School of Medicine then developed custom-built 'microarrays', or DNA chips, to identify which of the genes was abnormal in pancreatic cancer. Using this approach, the team hoped to pinpoint genes that were 'over-expressed' in cancerous pancreatic cells. 'We finally found what we had so doggedly pursued - a gene that was expressed 21 times more than any other', said Brentall.
The discovery means that it should now be possible to offer genetic testing to some families affected by pancreatic cancer. The team also hope to develop a blood test for all forms of pancreatic cancer, based on detecting the Palladin protein, as well as new therapies to treat the disease.