Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Subtle changes in normal genes implicated in breast cancer

14.07.2005


New search method could aid in the discovery of biomarkers



Using a super-efficient method they invented to search for a type of cancer-related change in all genes of a cell, Dana-Farber Cancer Institute researchers have discovered new evidence about how the "microenvironment" of breast cancers helps drive the cancers’ growth and migration.

The scientists found that non-cancerous cells surrounding young breast cancers -- the microenvironment -- undergo epigenetic modifications. (Epigenetic modifications affect genetic function and are passed along to the cell’s offspring, but they don’t alter a gene’s actual structure or DNA.) The subtly altered gene function causes the microenvironment cells to send signals to the breast tumor cells to grow fast and become more aggressive.


"This is the first demonstration that epigenetic occur in the supportive cells of a tumor, and this further emphasizes that surrounding cells play an active role in cancer formation and growth," says Kornelia Polyak, MD, PhD. "These changes in the microenvironment may occur before breast duct cells undergo genetic changes that cause cancer, thus detecting the epigenetic alterations may be a means of early cancer diagnosis or even predicting cancer risk."

Polyak is senior author of the paper, which was posted this week as an advance online publication on the Nature Genetics web site, http://www.nature.com/ng. The first author of the paper is Min Hu, PhD, of Dana-Farber.

Polyak and her colleagues had previously shown that the genes in the microenvironment surrounding the breast’s milk ducts were overactive, and that they continued to be overactive when their cells reproduced, even though their DNA had not been altered. She suspected that the methylation state of the cells’ DNA was being inherited. A gene’s activity can be regulated by a kind of chemical switch process, methylation, when units called methyl groups are added or removed from the gene’s DNA. The on-off pattern of methylation in a cell’s genes can be passed from one generation to another, even when the DNA remains unchanged. This is an example of an epigenetic modification.

Cancer is often associated with less-than-normal methylation of cells’ DNA. Techniques exist for checking the methylation state of a cell, gene by gene. But Polyak and her colleagues, looking to obtain the methylation pattern of a cell’s entire genome (approximately 20,000-25,000 genes) at once, devised a method called Methylation Specific Digital Karyotyping (MSDK) that can read a cell’s complete methylation profile. Polyak and her colleague obtained a profile of the entire genome in a few weeks, a task that would have taken several weeks to months, if it was even possible, using conventional methods.

Using MSDK to study breast cancer tissue, the scientists tested the epithelial and myoepithelial cells that line the breast ducts, and the surrounding cells, known as stoma, including fibroblasts. They found that in all of these cell types, gene expression was altered by epigenetic methylation changes that were not present in normal breast tissue cells.

Most breast cancers develop in the inner lining of the breast’s milk ducts. Some cancerous lesions remain confined within the ducts for years -- called ductal carcinoma in situ or DCIS. Others become invasive, breaking through the walls of the duct into the breast tissue, and threatening to metastasize throughout the body. In previous work, the Dana-Farber scientists showed that the stromal cells of the microenvironment, while not malignant themselves, can goad the cancer cells within the duct into more aggressive action. This insight, the researchers commented, provide a rationale for future chemotherapy that targets the stromal cells as well as the tumors themselves.

In addition to furthering scientific understanding of how breast cancers grow, the method and the new findings could aid in the discovery of biomarkers, or physical changes that could be used in the early detection of breast cancers before they can be diagnosed by conventional means.

Polyak said that Dana-Farber has filed for a patent on the method and the genes identified as aberrantly methylated in the various cell types, and is working with a company to use it for the development of diagnostic tools for early breast cancer diagnosis.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>