Laser capture microdissection facilitates colon-cancer discovery

FEBRUARY 6, 2009--Researchers at the University of Cincinnati (UC) have discovered genetic variations that may prove to be key predictors of risk for colon cancer and indicators of the cancer's progression. And MDS Analytical Technologies (Sunnyvale, CA), says its Arcturus Laser Capture Microdissection (LCM) instruments were key to the discovery.

"By maintaining custody of the sample throughout the microdissection process, the Arcturus system removed any guesswork from the experiment, and allowed the researchers at the University of Cincinnati to collect only their desired material for this important study," said Andy Boorn, President of MDS Analytical Technologies.

As reported in PLoS Genetics, the UC scientists used Arcturus systems to investigate the role that the abnormal regulation of a known prostate cancer biomarker--alpha-methylacyl-coenzyme A racemase (AMACR)--plays in colon cancer. AMACR is a protein that breaks down branched-chain fatty acids, which are found in red meats and dairy products, and are suspected to be risk factors for the disease.

"AMACR was recently shown to have abnormal expression patterns in colon cancer, but not much was known about how it's regulated at the gene level," said Shuk-mei Ho, Ph.D., Chair of UC's Department of Environmental Health and senior author of the study. "Uncovering how the gene is abnormally activated in cancer will give us a better understanding of how to treat the disease in the end."

To find answers, scientists at UC, along with researchers at the University of Massachusetts, used Arcturus LCM instruments to enrich a homogenous population of cancer cells from colon carcinoma tissue, so that their data would not be obscured by non-carcinoma material that otherwise would be included in the analysis. Scientists analyzed a series of samples that represented the entire colon cancer progression, comparing the genetic sequences of the laser capture microdissected colon carcinoma cells with sequences from a general population. Comparative sequencing of the two groups of samples revealed the genetic variations that may be the triggers for abnormal protein expression found in colon cancer.

"Only by using LCM were we able to uncover these deletions in the AMACR sequence," Dr. Ho said. "We needed to look at only the cancer cells versus normal cells, and LCM was the only way to achieve this level of sensitivity."

In addition to the novel deletions, the study identified putative transcription factors that, under normal circumstances, may bind to the deleted sequence to regulate gene expression. The study also found a novel genetic variant in AMACR that is present in the general population, and which may influence the course of how colon cancer may progress.

"We need to start paying closer attention to how the environment in which we live and the things we put in our bodies interact with our genetic makeup to influence our cancer risk," Dr. Ho added.

The UC research team expects to expand this research into a multi-center study in the near future. The project is currently funded by the National Institutes of Health and the U.S. Army Prostate Cancer Program.

Researchers hope that these important findings will provide doctors with much improved diagnostic tools for colon cancer. By identifying people that carry these genetic variations, doctors will be better equipped to determine the course of treatment for patients with the disease. This data may also prove important as doctors advise patients on health and lifestyle choices that may influence one's risk of developing the disease.

More information:
The paper, Deletion Hotspots in AMACR Promoter CpG Island Are cis-Regulatory Elements Controlling the Gene Expression in the Colon, in PLoS Genetics
MDS Analytical Technologies' Laser Capture Microdissection (LCM) systems

Posted by Barbara G. Goode, barbarag@pennwell.com.

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