LCM Tools Help in Discovery of Potential Colon-Cancer Biomarker

MDS Analytical Technologies’ Arcturus® Laser Capture Microdissection (LCM) tools have been helping researchers at the University of Cincinnati (UC) in their discovery of genetic variations that may prove to be key predictors of risk for colon cancer and indicators of the disease’s progression. As reported in PLoS Genetics*, scientists at UC have been investigating the role that the
abnormal regulation of a known prostate cancer biomarker – alpha-methylacylcoenzyme 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, PhD, 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.” Researchers at UC and the University of Massachusetts enriched a homogenous population of cancer cells from colon carcinoma tissue. They then analysed 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.” The study also identified putative transcription factors that, under normal circumstances, may bind to the deleted sequence to regulate gene expression,as well as a novel genetic
variant in AMACR present in the general population, which may influence the progression of colon cancer. “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. “MDS Analytical Technologies is very pleased that its Arcturus line of LCM instruments played such a key role in this important discovery that may move us even closer to preventing more people from developing colon cancer,” said Andy Boorn, President of
MDS Analytical Technologies. “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.” 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 US Army Prostate Cancer Program.

* PLoS Genetics, January 16, 2009. Published by the U.S.
Public Library of Science