First familial pancreatic cancer gene identified

December 11, 2006

Pancreatic cancer is relatively rare but deadly; most patients die within a year of diagnosis, and it is the fourth leading cause of cancer deaths in the US. At least 10% of pancreatic cancers are thought to be familial, i.e., caused by inherited genetic mutations. The responsible genes have so far remained elusive, but one of the research teams that had been on a pancreatic cancer gene hunt for years now reports success: Teri Brentnall (University of Washington), David Whitcomb (University of Pittsburgh), and colleagues publish the identification of the palladin gene as the one mutated in a large family they had been studying for a while.

Family X, as it is referred to, has 18 members from 4 generations who had either pancreatic cancer or precancerous lesions of the pancreas. Tracing the DNA segments that are shared by these patients but not present in the healthy family members, the researchers had previously mapped the gene to a relatively small region of chromosome 4, which contains 243 known genes. They then made a gene chip that can measure expression levels of these 243 candidate genes and compared normal pancreas tissue with cancerous pancreas (both from a Family X member and from unrelated patients with pancreatic cancer).

Palladin, one of the 243 genes, turned out to be abnormally highly expressed in both the Family X tissue and the sporadic cancers. Named after the 16th century Italian architect Palladio, palladin codes for a component of the cytoskeleton (the scaffold that helps to control cell shape and motility). Next, the researchers quantified the expression of palladin RNA in an independent set of normal and cancerous pancreatic samples, and in precancerous pancreatic tissue taken from family X members. This analysis indicated that palladin was overexpressed early in sporadic and inherited pancreatic cancer development. Sequencing of the palladin gene then uncovered a mutation in palladin that was present in Family X members with pancreatic cancer or precancerous lesions but not in unaffected members. Finally, the researchers showed that the introduction of mutated palladin into a human cell line growing in the laboratory increased its migration rate and disrupted its cytoskeleton (both features typical of cancer cells).

These results leave little doubt that mutated palladin is involved in the development of pancreatic cancer in Family X. Moreover, they suggest that overexpression of palladin is also associated with and possibly responsible for a sizeable proportion of sporadic pancreatic cancers. The identification of palladin as a "pancreatic cancer gene" provides researchers with a molecular entry point into the cellular processes underlying this cancer and will hopefully help to improve diagnosis and development of new treatments for this deadly disease.
-end-
* * * * * * * EMBARGO: MONDAY, 11 December, 5 P.M. PST * * * * * * *

PLEASE MENTION THE OPEN-ACCESS JOURNAL PLoS MEDICINE (www.plosmedicine.org) AS THE SOURCE FOR THESE ARTICLES AND PROVIDE A LINK TO THE FREELY-AVAILABLE TEXT. THANK YOU.

All works published in PLoS Medicine are open access. Everything is immediately available without cost to anyone, anywhere--to read, download, redistribute, include in databases, and otherwise use--subject only to the condition that the original authorship is properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.

Citation: Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, White Moyes K, et al. (2006) Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med 3(12): e516.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0040516

PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-03-12-brentnall1.pdf

Related Image for press use: http://www.plos.org/press/plme-03-12-brentnall1.jpg

Caption: Mutated cytoskeletal protein, Palladin, causes pancreatic cancer. Please credit to the laboratory of Teri Brentnall

Related Image for press use: http://www.plos.org/press/plme-03-12-brentnall2.jpg

Caption: Mutated cytoskeletal protein, Palladin, causes pancreatic cancer. Please credit to the laboratory of Teri Brentnall

CONTACT:
Clare Hagerty
University of Washington
+1 206-685-1323
clareh@u.washington.edu

David Whitcomb
University of Pittsburgh
+1 412-648-9604
whitcomb@pitt.edu

About PLoS Medicine

PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org

PLOS

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.