JWCI Researchers Identify Genetic Changes That Occur As Normal Tissue Progresses to Colon Cancer
In a first-of-its-kind study, researchers at Santa Monica, CA-based John Wayne Cancer Institute at Saint John’s Health Center have successfully identified environmental influencers that change gene activity as healthy colorectal tissue transforms to abnormal tissue (benign) and eventually progresses to colorectal cancer.
The study involved using new approaches at the ultramicroscopic level to identify very early stages of benign tissue that eventually developed into cancer. The study findings are now being validated in a collaboration with a larger ongoing investigation of colorectal cancer by the Dutch Colorectal Cancer Group (DCCG) multicenter study group, which eventually will report on the relation of findings to disease outcome. Combined, the two studies could have important implications to the early identification of benign disease developing to colorectal cancer, prevention of disease progression in those who are at risk, prediction of disease outcome, and identifying targets for treatment, said Dave S.B. Hoon, Ph.D., an investigator for the Santa Monica study. Hoon also is a principal investigator for the Dutch translational study collaboration, the results for which may be released as soon as this year.
Findings from the Saint John’s/John Wayne Cancer Institute study were published in a cover peer-review article for the translational cancer journal Molecular Cancer Research, a publication of the American Association of Cancer Research titled “Assessment of Methylation Events During Colorectal Tumor Progression by Absolute Quantitative Analysis of Methylated Alleles.” The article was authored by Michiel F.G. deMaat (Dutch group) and co-authored by Dr. Roderick R. Turner and Hoon, who is a researcher with the Department of Molecular Oncology at JWCI. Dr. Roderick R. Turner represents the Department of Surgical Pathology at Saint John’s.
“What we did was identify specific environmental influencers that occur as colorectal normal tissue evolves to benign and eventually into colorectal cancer,” Hoon said. “There is a class of new drugs being investigated that are targeted to these changes to actually reverse them. Identifying such changes at the microscopic level, before they turn into cancer, can potentially enable us to develop strategies to prevent and diagnose early on the development of malignant tumors in the colon and rectum.”
Hoon added that results of the study combined with the eventual results of the Dutch study could enable cancer disease outcome to be more accurately predicted in patients and improve approaches into specific treatments.
“These results are quite important,” Hoon said. “We were able to use archival tissue samples and laser microdissection to isolate at the ultramicroscopic level a very small number of cells from abnormal lesions, and detect these quantitative genetic changes–which couldn’t be done before. By using our unique approach, we were able to better assess early microscopic changes from normal tissue to benign to cancer using archival tissues. The collection of these archival tissues has allowed us to successfully move the field forward.”
The American Cancer Society has predicted that more than 150,000 new cases of colorectal cancer will be diagnosed in the U.S. during 2007. An estimated 35,000 of those patients–nearly 25%–are expected to die from the disease.
Implications of the study could be enormous. Research by the John Wayne Cancer Institute, Saint John’s Health Center and the Dutch Colorectal Cooperative group would develop better biomarkers to identify the likely fate of patients as well as potential therapeutic targets for preventive treatment.