Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Wistar Scientists Develop Gene Test to Accurately Classify Brain Tumors

19.02.2014
Computer Model of Gene Transcript Variants May Aid Doctors in Personalizing Therapies

Scientists at The Wistar Institute have developed a mathematical method for classifying forms of glioblastoma, an aggressive and deadly type of brain cancer, through variations in the way these tumor cells “read” genes.

Their system was capable of predicting the subclasses of glioblastoma tumors with 92 percent accuracy. With further testing, this system could enable physicians to accurately predict which forms of therapy would benefit their patients the most.

Their research was performed in collaboration with Donald M. O’Rourke, M.D., a neurosurgeon at the University of Pennsylvania Brain Tumor Center, who provided the glioblastoma samples necessary to validate the Wistar computer model. Their findings were published online in the journal Nucleic Acids Research.

“It has become increasingly obvious that understanding the molecular makeup of each patient tumor is the key to personalizing cancer treatments for individual patients,” said Ramana Davuluri, Ph.D., Wistar’s Tobin Kestenbaum Family Professor and associate director of Wistar’s Center for Systems and Computational Biology. “We have developed a computational model that will allow us to predict a patient’s exact variety of glioblastoma based on the transcript variants a given tumor produces.”

“A gene can produce multiple variants, in the form of transcript variants and protein-isoforms. We found that when you use the gene expression information at variant/isoform-level, the statistical analyses recaptured the four known molecular subgroups but with a significant survival difference among the refined subgroups.” said Davuluri. “Using patient data, we found that certain subgroups when combined with patient age, for example, could predict better outcomes using a given course of therapy.”

“As more targeted therapies come into use, this is exactly the sort of information clinicians will need to provide the best hope of survival for their patients,” Davuluri said. “In time, we think this could form the basis of a clinical test that will help oncologists decide a patient’s course of treatment.”

Glioblastoma multiforme is the most lethal of the malignant adult brain tumors, and accounts for over 50 percent of all cases of brain cancer. Even with aggressive combination therapies, the prognosis remains bleak, with median patient survival of 15 months after diagnosis. The disease is also molecularly heterogeneous, that is, composed of subtypes that are not genetically alike or produce the same array of proteins. Genetic data from the Cancer Genome Atlas (TCGA) consortium has led to the identification of four subtypes of glioblastoma, but Davuluri and his researchers sought to find a way to quickly identify which patient was which subtype.

In previous studies, Davuluri and his Wistar colleagues have established how changes in the way a cell reads its own DNA can create multiple variations of a single protein. These variant proteins are called isoforms, and they are produced as cells alter how they transcribe a given gene into RNA. Slight changes in how the cellular machine reads a gene can result in protein isoforms with subtle differences in enzymatic activity or longevity.

For example, their earlier research determined how human brains produce different isoforms of specific proteins throughout their lives. Developing fetal brains produce different isoforms of certain genes than adult brains. They also found that changes that trigger the production of the wrong isoform at the wrong time could lead to cancer.

In the Nucleic Acids Research study, the researchers combined assays of these protein isoforms with a computer model they call PIGExClass, or the Platform-independent Isoform-level Gene-EXpression based Classification-system. To categorize glioblastomas with PIGExClass, Davuluri and his colleagues first began with Cancer Genome Atlas data to develop a set of 121 isoform variants whose combination of differences could denote a specific subtype of the brain cancer. PIGExClass is, essentially, a software that ranks gene isoform data into sets based on a set of pre-determined values. The researchers found that, by using this classification system, they could predict the subtype of glioblastoma in the database with 92 percent accuracy.

“When we knew what combination of isoforms could create a specific signature for each type of glioblastoma, we could then create a simple laboratory assay that would look for these differences in patient samples,” Davuluri said. “In this case the test would measure variations in the RNA abundance associated with these 121 isoforms that make up the signature.”

With this new assay in hand, the researchers validated their research using 206 independent samples from the University of Pennsylvania Brain Tumor Tissue Bank. According to Davuluri, when you accounted for differences in the makeup of the pools of patients between TCGA and Penn, the accuracy of the assay remained the same.

Co-authors include Luke Macyszyn, M.D., a neurosurgery resident at the University of Pennsylvania, and Wistar scientists Sharmistha Pal, Ph.D., Yingtao Bi, Ph.D., and Professor Louise C. Showe, Ph.D. This study was partially funded by the National Institutes of Health [award number R01LM011297].

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures.

Greg Lester | EurekAlert!
Further information:
http://www.wistar.org

More articles from Health and Medicine:

nachricht Discovery points to a new path toward a universal flu vaccine
03.07.2015 | Rockefeller University

nachricht "CCS Telehealth Ostsachsen", Germany's largest telemedicine project, goes online in Dresden
02.07.2015 | Universitätsklinikum Carl Gustav Carus Dresden

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Siemens receives order for offshore wind power plant in Great Britain

03.07.2015 | Press release

'Déjà vu all over again:' Research shows 'mulch fungus' causes turfgrass disease

03.07.2015 | Agricultural and Forestry Science

Discovery points to a new path toward a universal flu vaccine

03.07.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>