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Scientists identify more than 500 genes that may cause pancreatic cancer

Date:
March 12, 2012
Source:
Methodist Hospital, Houston
Summary:
Scientists have identified more than 500 genes that may cause or contribute to the development of pancreatic cancer. This particularly deadly disease has a 1-in-20 survival rate after five years, largely because no effective genetic screening method exists for early detection.

A global team led by scientists from The Methodist Hospital Research Institute has identified more than 500 genes that may cause or contribute to the development of pancreatic cancer. This particularly deadly disease has a 1-in-20 survival rate after five years, largely because no effective genetic screening method exists for early detection.

Principal investigators Nancy Jenkins, Ph.D., and Neal Copeland, Ph.D., report in the Proceedings of the National Academy of Sciences, online soon, that the vast majority of the 543 genes they identify in mouse models have identical or highly similar versions in humans, and that 20 of those equivalent genes were found to be strongly associated with poor survival in human pancreatic cancer patients.

"Knowing what genes are involved in the development of pancreatic cancer, as well as what those genes' functions are and how they influence signaling pathways, will be crucial to the development of new drugs and other therapies," said Copeland, director of the Methodist Cancer Research Program and a National Academy of Sciences fellow.

The scientists show in the PNAS paper that many of the new pancreatic cancer candidate genes are associated with signaling and metabolic pathways that influence cell-to-cell communication, division, and the protection of the cell's chromosomal DNA, and are therefore plausible cancer genes.

The work described corroborates single-gene work done in humans, and vice versa, and could help people find out whether they are at risk for developing the disease, he said.

The kind of pancreatic cancer the scientists were studying is called pancreatic ductal adenocarcinoma, and is the most common type of pancreatic cancer. Among all cancers, this type of cancer is the 4th deadliest. Only one in four patients diagnosed with this survive a year, and one in 20 are alive after five years.

Jenkins and Copeland emphasize the importance of developing new tools to identify people who at risk for developing pancreatic cancers, so people and their doctors can be more vigilant about the development of the disease, as well as developing biomarkers that can tell pathologists when the disease has begun, and how aggressive it is likely to be.

"Understanding all the genes that influence pancreatic cancer will ultimately impact personalized medicine," said Jenkins, co-director of the Methodist Cancer Research Program and also a National Academy of Sciences fellow. "You'll be able to say, in patients, their risk is low or high because of the specific versions of these genes they have in their own genomes, which will also impact what kinds of therapies will be most effective for them. What we're reporting represents some of the first steps."

Jenkins and Copeland developed a mouse model with a genome that has about 350 copies of a transposon called Sleeping Beauty (SB). Transposons are moveable genetic elements that are normally dormant, but can be induced to move locations. When the SB transposon moves, it may end up anywhere else in the genome -- even in the middle of important genes, disrupting the genes' functions.

The scientists activated SB only in pancreas cells, then looked for individual mice that had developed pancreatic tumors.

Genomic analysis of the tumor cells and the digestion of data using two statistical methods revealed 681 transposon-induced mutations in 543 genes. Mutations in 75 of these genes have previously been implicated in pancreatic cancer -- but 468 have not. 20 of the newly discovered candidate genes were strongly associated with high mortality in human pancreatic patients, and 11 were found to have point mutations in human patients.

About 10 percent of the candidate genes are involved in chromatin remodeling, a routine process in the cell nucleus that affects the availability of genes for expression.

Jenkins and Copeland, who joined The Methodist Hospital Research Institute last year, were at the Institute of Molecular and Cell Biology in Singapore when this research was conducted. They are married -- and long-time collaborators in science, as well.

Also contributing to this work were Karen Mann (TMHRI); Jerrold Ward and Christopher Chin Kuan Yew (Institute of Molecular and Cell Biology, Singapore); Anne Kovovich and David Dawson (UCLA David Geffen School of Medicine); Michael Black (University of Otago, New Zealand); Benjamin Brett, Todd Sheetz, and Adam Dupuy (University of Iowa); researchers at the Australian Pancreatic Cancer Genome Initiative; David Chang, Andrew Biankin, Nicola Waddell, and Karin Kassahn (University of New South Wales Medicine, Australia); and Alistair Rust and David Adams (University of Queensland Institute for Molecular Bioscience, Australia).

The research was funded by grants from Biomedical Research Council, Agency for Science, Technology, and Research, Singapore; the National Health and Medical Research Council of Australia; the Queensland Government; the Cancer Council New South Wales; the Cancer Institute New South Wales; the Royal Australian College of Surgeons; the Australian Cancer Research Foundation; the St. Vincent's Clinic Foundation, the Avner Nahmani Pancreatic Cancer Foundation, and the R.T. Hall Trust.


Story Source:

The above story is based on materials provided by Methodist Hospital, Houston. Note: Materials may be edited for content and length.


Cite This Page:

Methodist Hospital, Houston. "Scientists identify more than 500 genes that may cause pancreatic cancer." ScienceDaily. ScienceDaily, 12 March 2012. <www.sciencedaily.com/releases/2012/03/120312152643.htm>.
Methodist Hospital, Houston. (2012, March 12). Scientists identify more than 500 genes that may cause pancreatic cancer. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2012/03/120312152643.htm
Methodist Hospital, Houston. "Scientists identify more than 500 genes that may cause pancreatic cancer." ScienceDaily. www.sciencedaily.com/releases/2012/03/120312152643.htm (accessed August 1, 2014).

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