US researchers pinpoint inherited pancreatic cancer gene

In collaboration with the Press Association

Researchers have discovered that inheriting a faulty copy of a gene called Palladin can cause familial pancreatic cancer. The international team of researchers published their findings in PLoS-Medicine in which they explain that when the Palladin gene is functioning properly, it produces a protein that helps gives a cell its shape and enables the cell to move. In the case of pancreatic cancer, a mutation in the Palladin gene allows the cell to move much more freely than normal, allowing it to invade the surrounding healthy tissue. It is believed that the mutated Palladin causes cancer by causing the cytoskeleton, the structural backbone of human cells to malfunction, which allows the cells to move much more quickly than normal cells. "A normal cytoskeleton holds up the cell wall, and gives it direction to sit down in its proper place and basically to behave," said Dr Teri Brentnall, University of Washington associate professor of medicine. "In cancerous cells, the cytoskeleton doesn't work correctly, and instead of sitting, the cells get up and invade areas where they don't belong, which is how the cancer spreads. This is a new way of thinking about cancer development in the pancreas." The hunt for the gene started in 1996, when one of Dr Brentnall's patients described pancreatic cancer as "his family's curse".

His grandfather, father, four uncles and three cousins had all died of pancreatic cancer, some at a very young age. Brentnall designated this family as "Family X" and set off to identify the source of the fatal inheritance. The puzzle took a decade to unravel.

"By performing surveillance on many of the Family X members, the research team identified which ones had the initial stages of pancreatic cancer," said Dr Brentnall. "We then compared DNA samples from the family members with pre-cancer to those who did not have the disease, and isolated the cancer-causing gene to an area of Chromosome 4." They eventually homed in on Palladin - a previously known gene. "This gene, Palladin, was mutated in Family X and appeared to cause the fatal inheritance. Every one of the members of Family X who had the Palladin mutation got pancreatic cancer or pre-cancer, while the members of Family X who did not have the mutation were cancer-free," Dr Brentnall said.

The hope is that this discovery will shed light on how pancreatic cancer develops in people who do not inherit a faulty copy of the gene.

Pancreatic cancer is notoriously hard to treat. There are over 7,100 cases of the disease, and 7,000 deaths, in the UK each year.