Featured Research

from universities, journals, and other organizations

Subtle Changes In Normal Genes Implicated In Breast Cancer

Date:
July 14, 2005
Source:
Dana-Farber Cancer Institute
Summary:
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.

BOSTON--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.

###

In addition to Polyak and Hu, the paper's other authors are Jun Yao, PhD, and Li Cai, MD, PhD, Dana-Farber; Kurt E. Bachman, PhD, University of Maryland; Frederic van den Brule, MD, PhD, University of Liege, Belgium; and Victor Velculescu, MD, PhD, Johns Hopkins University.

The research was supported by a SPORE grant from the National Cancer Institute to the Dana-Farber/Harvard Cancer Center, and grants from the Department of Defense and the American Cancer Society.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Subtle Changes In Normal Genes Implicated In Breast Cancer." ScienceDaily. ScienceDaily, 14 July 2005. <www.sciencedaily.com/releases/2005/07/050714003719.htm>.
Dana-Farber Cancer Institute. (2005, July 14). Subtle Changes In Normal Genes Implicated In Breast Cancer. ScienceDaily. Retrieved August 31, 2014 from www.sciencedaily.com/releases/2005/07/050714003719.htm
Dana-Farber Cancer Institute. "Subtle Changes In Normal Genes Implicated In Breast Cancer." ScienceDaily. www.sciencedaily.com/releases/2005/07/050714003719.htm (accessed August 31, 2014).

Share This




More Health & Medicine News

Sunday, August 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins