Featured Research

from universities, journals, and other organizations

New analysis reveals tumor weaknesses in epigenetics

Date:
August 12, 2014
Source:
Massachusetts Institute of Technology
Summary:
Epigenetic markers in cancer cells could improve patient treatment, researchers report. Scientists have known for decades that cancer can be caused by genetic mutations, but more recently they have discovered that chemical modifications of a gene can also contribute to cancer. These alterations, known as epigenetic modifications, control whether a gene is turned on or off.

Scientists have known for decades that cancer can be caused by genetic mutations, but more recently they have discovered that chemical modifications of a gene can also contribute to cancer. These alterations, known as epigenetic modifications, control whether a gene is turned on or off.

Related Articles


Analyzing these modifications can provide important clues to the type of tumor a patient has, and how it will respond to different drugs. For example, patients with glioblastoma, a type of brain tumor, respond well to a certain class of drugs known as alkylating agents if the DNA-repair gene MGMT is silenced by epigenetic modification.

A team of MIT chemical engineers has now developed a fast, reliable method to detect this type of modification, known as methylation, which could offer a new way to choose the best treatment for individual patients.

"It's pretty difficult to analyze these modifications, which is a need that we're working on addressing. We're trying to make this analysis easier and cheaper, particularly in patient samples," says Hadley Sikes, the Joseph R. Mares Assistant Professor of Chemical Engineering and the senior author of a paper describing the technique in the journal Analyst.

The paper's lead author is Brandon Heimer, an MIT graduate student in chemical engineering.

Beyond the Genome

After sequencing the human genome, scientists turned to the epigenome -- the chemical modifications, including methylation, that alter a gene's function without changing its DNA sequence.

In some cancers, the MGMT gene is turned off when methyl groups attach to specific locations in the DNA sequence -- namely, cytosine bases that are adjacent to guanine bases. When this happens, proteins bind the methylated bases and effectively silence the gene by blocking it from being copied into RNA.

"This very small chemical modification triggers a sequence of events where that gene is no longer expressed," Sikes says.

Current methods for detecting cytosine methylation work well for large-scale research studies, but are hard to adapt to patient samples, Sikes says. Most techniques require a chemical step called bisulfite conversion: The DNA sample is exposed to bisulfite, which converts unmethylated cytosine to a different base. Sequencing the DNA reveals whether any methylated cytosine was present.

However, this method doesn't work well with patient samples because you need to know precisely how much methylated DNA is in a sample to calculate how long to expose it to bisulfite, Sikes says.

"When you have limited amounts of samples that are less well defined, it's a lot harder to run the reaction for the right amount of time. You want to get all of the unmethylated cytosine groups converted, but you can't run it too long, because then your DNA gets degraded," she says.

Rapid Detection

Sikes' new approach avoids bisulfite conversion completely. Instead, it relies on a protein called a methyl binding domain (MBD) protein, which is part of cells' natural machinery for controlling DNA transcription. This protein recognizes methylated DNA and binds to it, helping a cell to determine if the DNA should be transcribed.

The other key component of Sikes' system is a biochip -- a glass slide coated with hundreds of DNA probes that are complementary to sequences from the gene being studied. When a DNA sample is exposed to this chip, any strands that match the target sequences are trapped on the biochip. The researchers then treat the slide with the MBD protein probe. If the probe binds to a trapped DNA molecule, it means that sequence is methylated.

The binding between the DNA and the MBD protein can be detected either by linking the protein to a fluorescent dye or designing it to carry a photosensitive molecule that forms hydrogels when exposed to light.

The MIT team is now adapting the device to detect methylation of other cancer-linked genes by changing the DNA sequences of the biochip probes. They also hope to create better versions of the MBD protein and to engineer the device to require less DNA. With the current version, doctors would need to do a surgical biopsy to get enough tissue, but the researchers would like to modify it so the test could be done with just a needle biopsy.


Story Source:

The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton. Note: Materials may be edited for content and length.


Journal Reference:

  1. Brandon W. Heimer, Tatyana A. Shatova, Jungkyu K. Lee, Kaja Kaastrup, Hadley D. Sikes. Evaluating the sensitivity of hybridization-based epigenotyping using a methyl binding domain protein. The Analyst, 2014; 139 (15): 3695 DOI: 10.1039/C4AN00667D

Cite This Page:

Massachusetts Institute of Technology. "New analysis reveals tumor weaknesses in epigenetics." ScienceDaily. ScienceDaily, 12 August 2014. <www.sciencedaily.com/releases/2014/08/140812163531.htm>.
Massachusetts Institute of Technology. (2014, August 12). New analysis reveals tumor weaknesses in epigenetics. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2014/08/140812163531.htm
Massachusetts Institute of Technology. "New analysis reveals tumor weaknesses in epigenetics." ScienceDaily. www.sciencedaily.com/releases/2014/08/140812163531.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
Powered by NewsLook.com
Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Despite Rising Death Toll, Many Survive Ebola

Despite Rising Death Toll, Many Survive Ebola

AP (Oct. 23, 2014) The family of a Dallas nurse infected with Ebola in the US says doctors can no longer detect the virus in her. Despite the mounting death toll in West Africa, there are survivors there too. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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