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Study of genomic DNA leads to new advances in cancer diagnostics

Researchers at the University of Illinois at Chicago have identified a method of assessing the malignant potential of cells based on the sensitivity of cellular DNA to enzyme digestion. The article by Andrew J. Maniotis et al., "Chromatin sensitivity to Alu I restriction enzyme decreases with malignancy and is regulated by the extracellular matrix and cytoskeleton," appears in the April 2005 issue of The American Journal of Pathology and is accompanied by a commentary.

Using an enzyme (Alu I) that cuts DNA at a common sequence in the human genome, Dr. Maniotis's group classified cells based on sensitivity or resistance to DNA digestion. Non-malignant cells were sensitive to DNA digestion by Alu I while highly malignant cells were resistant. These results suggest that a cell's DNA, or chromatin, is protected during malignancy. This effect was confirmed using three pairs of cell types (normal melanocytes and melanoma cells, normal breast epithelium and breast carcinoma cells, and normal fibroblasts and fibrosarcoma cells) and diagnostic biopsy samples.

Will these methods help clinicians in diagnosing cancer? Because the investigators utilized several practical methods in their study, potential exists for future diagnostic applications. The cell smear assay, which is similar to methods commonly used in diagnostics laboratories (such as Pap smears), could be applied to such a purpose. The authors also used flow cytometry to characterize melanomas of varying invasiveness. Further study will be required to determine the specificity and sensitivity of these methods before they are used in the clinical setting.

Physicians and researchers alike know that how a cancer cell interacts with its microenvironment is important for cancer progression. Such interactions must be aberrant for abnormal cell growth and metastasis to occur. Indeed, Dr. Maniotis and his colleagues found that the extracellular matrix (ECM), or the microenvironment surrounding the cell
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Source:The American Journal of Pathology


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