A Pancreatic Cancer Surveillance study on the leading-edge of familial pancreatic cancer research,
led by Dr. Teresa Brentnall and her nationwide team of collaborators, has attracted its share of attention throughout
a ten-year span. The product of this groundbreaking research, discovery of a genetic cause of familial pancreatic cancer,
was recently published in the December 12 issue of the medical journal
PLoS (Public Library of Science). The story was also featured in the
December 12 issue of USA Today.
Read Official Press Release |
Learn More About Genetic Testing
PLoS-Medicine Article |
USA Today Article |
Seattle Times Article
Seattle Post-Intelligencer Article
Palladin gene testing might be appropriate for families with 2 or more members with pancreatic cancer. PLEASE NOTE: The test is not
yet available for clinical use. Stay tuned for future information regarding this test.
Dr. Brentnall has devoted herself to better understanding the risks and biological mechanisms involved in familial pancreatic
cancer since the very day a 41-year old man presented to her office with grave concern about developing the disease due to an
extensive family history. The family (known as ‘Family X’) served as the inspiration for Dr. Brentnall’s
Pancreatic Cancer Surveillance Study, which has been tracking high-risk
patients in an effort to improve early detection methods and working to identify gene(s) responsible for causing the familial disease.
For years, growing evidence has suggested that a genetic susceptibility may predispose people to pancreatic cancer.
Currently, two or more family members are affected in at least 10% of all pancreatic cancer cases – and risk increases with
each affected family member. Genetic susceptibility is also suspected in many “sporadic,” or non-familial, forms of the disease.
Dr. Brentnall and her team set out to discover the gene in ‘Family X’ that caused pancreatic cancer to be inherited in the family.
The result was identification of an unknown gene located on a small region of
To discover exactly what the gene was, Dr. Brentnall and her team studied the expression of all the genes in the Chromosome 4 region
in the pre-cancerous pancreas from ‘Family X’ and from 10 sporadic pancreatic cancer samples. The researchers assumed that the genetic
information encoded in a gene is switched ‘on’ at certain times and ‘speaks out’ in pre-cancer and cancer. Using sophisticated DNA
profiling techniques, the researchers compared gene expression among ‘Family X’ pre-cancerous tissue, normal pancreatic tissue, and
diseased tissue from sporadic pancreatic cancers. The analysis revealed that a gene, Palladin, a cytoskeletal protein that helps control
cell structure and mobility, was highly over-expressed in both ‘Family X’ tissue and all 10 of the sporadic pancreatic cancer tissues.
They went on to show that abnormal Palladin expression occurs very early during stages of disease development.
The team found a mutation in Palladin was present only in ‘Family X’ members with pancreatic cancer or precancerous lesions – and not
in unaffected family members. Although this specific mutation was not found in sporadic pancreatic cancers, most of the sporadic
pancreas cancers studied illustrated abnormal expression of Palladin– suggesting that Palladin may also play a role in the development
of sporadic pancreatic cancer. The researchers discovered that the abnormal expression of Palladin allows cells to become increasingly
mobile, a key feature of cancer cells.
Although further investigation is necessary to examine Palladin mutations in other high-risk families and explain its abnormal
expression in sporadic cases, Dr. Brentnall’s discovery is unlocking a key to our understanding of familial pancreatic cancer and
blazing a path for future avenues of research into