Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New analysis reveals tumor weaknesses

13.08.2014

Identifying epigenetic markers in cancer cells could improve patient treatment

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.

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.

###

The research was funded by a David H. Koch fellowship, a National Science Foundation fellowship, a Burroughs Wellcome Fund Career Award, the National Institute for Environmental Health Sciences, and the James H. Ferry Fund for Innovation.

Written by Anne Trafton, MIT News Office

Andrew Carleen | Eurek Alert!

Further reports about: DNA MIT cytosine method methylated methylation modification modifications require respond sequence sequences

More articles from Life Sciences:

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>