Navigation Links
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 , influenced whether the cell's chromatin was sensitive or resistant to Alu I. The group also implicated the cell's cytoskeleton, the internal scaffolding that gives the cell its shape, in this process. Changes to the ECM and cytoskeleton are critical to migration of a cancer cell from one site in the body to another.

The researchers could alter the Alu I sensitivity of a cell's chromatin by exposing the cell to a single extracellular matrix molecule or by disrupting any of three cytoskeletal systems, which link the outside of the cell to the genome. Using this information, Dr. Maniotis's group developed a new kind of extracellular matrix chip (patent pending) that is being used to study drug-resistance mechanisms to develop new protocols and methods to treat cancer.

Ultimately, the cellular changes that occur during cancer formation affect how the cell interacts with its microenvironment (ECM) and direct changes to the cytoskeleton and finally to the chromatin. Such changes can now be measured directly at the chromatin level. These findings may provide the basis for the design of a new generation of cancer therapeutic agents.

Research was funded by the National Institute of Health and the Department of Energy.

This work involved collaborators at the University of Illinois at Chicago Department of Pathology, the University of Illinois at Chicago Cancer Center, the University of Illinois at Chicago Core Genomics Facility, and the Lawrence Berkeley National Laboratory Life Sciences Division.

Maniotis AJ, Valyi-Nagy K, Karavitis J, Moses J, Boddipali V, Wang Y, Nuñez R, Setty S, Arbieva Z, Bissell MJ, and Folberg R: Chromatin organization measured by Alu I restriction enzyme changes with malignancy and is regulated by the extracellular matrix and the cytoskeleton. Am J Pathol 2005, 166: 1187-1203


'"/>

Source:The American Journal of Pathology


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/15/2016)... BADEN-BADEN, Germany , December 15, 2016 /PRNewswire/ ... services provider, today announced an agreement with NuData Security, ... join forces. The partnership will enable clients to focus on ... with local data protection regulation. ... In order to provide a one-stop ...
(Date:12/15/2016)... Dec. 15, 2016  There is much more to ... starting the engine. Continental will demonstrate the intelligence of ... Vegas . Through the combination of the keyless ... and biometric elements, the international technology company is opening ... and authentication. "The integration of biometric elements ...
(Date:12/8/2016)... 8, 2016  Singulex, Inc., the leader in Next ... into a license and supply agreement with Thermo Fisher ... provides Singulex access to Thermo Scientific BRAHMS PCT (Procalcitonin), ... is used to diagnose systemic bacterial infection and sepsis ... to aid in assessing the risk of critically ill ...
Breaking Biology News(10 mins):
(Date:1/23/2017)... NEW YORK , Jan. 23, 2017  Spherix ... development company committed to the fostering of technology and ... its active patent infringement lawsuits. Anthony ... we enter 2017, we will continue to communicate with ... Equitable IP and our due diligence on other patent ...
(Date:1/23/2017)... , Jan. 23, 2017 /PRNewswire/ - Resverlogix Corp. ("Resverlogix" ... from the New Zealand based ... The data showed remarkable results in reducing inflamed protein ... control patients. It is believed that this is the ... of this type can be made between epigenetic regulation ...
(Date:1/23/2017)... ... January 23, 2017 , ... Calvert Labs, Inc. announced today ... Senior Director, Safety Pharmacology. Dr. Thomas earned his M.Sc. and Ph.D. in ... as an academic and industry preclinical drug developer spans more than three decades. ...
(Date:1/23/2017)... ... January 23, 2017 , ... AxioMed will be ... (CANS) annual meeting in Montego Bay, Jamaica from January 26-28th. “We’re excited to ... for surgeons to experience the simplicity of the surgical technique,” said Jake Lubinski, ...
Breaking Biology Technology: