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:3/16/2017)... -- CeBIT 2017 - Against identity fraud with DERMALOG solutions "Made in ... ... Used combined in one project, multi-biometric solutions provide a crucial contribution against identity fraud. (PRNewsFoto/Dermalog ... Used combined in one project, multi-biometric solutions provide ... ...
(Date:3/7/2017)... Brandwatch , the leading social intelligence company, today announces that ... uncover insights to support its reporting, help direct future campaigns, and ... youth charity will be using Brandwatch Analytics social listening and analytics ... of the topics and issues that are a priority for its ... "Until recently ...
(Date:3/2/2017)... -- Summary This report provides all the ... its partnering interests and activities since 2010. Download ... Partnering Deals and Alliance since 2010 report provides an ... the world,s leading life sciences companies. On ... inclusion of the most up to date deal and ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... MENLO PARK, Calif., March 23, 2017  BioPharmX ... developing products for the dermatology market, today reported ... Jan. 31, 2017, and will provide an update ... from the year. "We are pleased ... productive year for BioPharmX," said President Anja Krammer. ...
(Date:3/23/2017)... -- NetworkNewsWire Editorial Coverage  ... Cancer remains one of the ... care systems, in terms of costs and resources. However, as ... development of innovative and efficient therapies that demonstrate higher chances ... of cancer treatments, a growing number of patients receiving immuno-oncology ...
(Date:3/23/2017)... YORK , March 23, 2017 ... look at four equities in the Biotech industry: Sangamo ... Synthetic Biologics Inc. (NYSE MKT: SYN), and Regulus Therapeutics ... 21 st , 2017, Credit Suisse upgraded its rating on ... by downloading their free report at: ...
(Date:3/22/2017)... ... March 22, 2017 , ... ... regeneration from small lab samples to full-size tissues, bones, even whole organs to ... vascular system that delivers blood deep into the developing tissue. , Current ...
Breaking Biology Technology: