Biomarker may help predict aggressive cancers

November 5, 2013

For children with central nervous system cancers, the presence of a specific genetic modification—hypermethylation of the TERT promoter—may help predict tumor progression and patient survival, according to results presented here at the American Association for Cancer Research (AACR) special conference on "Pediatric Cancer at the Crossroads: Translating Discovery Into Improved Outcomes," held Nov. 3-6.

The protein TERT is a component of the enzyme telomerase, which is found at elevated levels in the majority of cancers. Although this makes telomerase and its components potential biomarkers for cancer, there are currently no sensitive and specific methods for measuring levels of these candidates.

"DNA methylation controls gene usage," said Uri Tabori, M.D., a staff oncologist at The Hospital for Sick Children in Toronto. "We decided to examine whether there were different patterns of DNA methylation in an area of the genome that controls TERT expression in cancer cells and normal cells."

"We found that a region of DNA near the TERT gene was hypermethylated in 100 percent of the malignant tissues expressing TERT that we examined and unmethylated in normal tissues and in low-grade tumors lacking TERT. Although these results are restricted to pediatric cancers, we believe that this hypermethylation signature could be a pancancer biomarker because TERT levels are elevated in almost every cancer cell."

Tabori and colleagues began by conducting whole-genome methylation arrays on 280 pediatric brain tumor (from pediatric gliomas, ependymomas, choroid plexus tumors, medulloblastomas, and atypical teratoid-rhabdoid tumors) and six normal brain tissue samples. To validate their findings, they used 219 tissue samples from multiple types of pediatric central nervous system cancer.

The data revealed that a specific region of the TERT gene was hypermethylated in 100 percent of the malignant tumor tissue samples expressing TERT. In addition, hypermethylation of this region of DNA, which the researchers termed the TERT hypermethylated oncological region, or the THOR, was able to distinguish malignant tumor tissue samples from normal tissue and low-grade tumor tissue samples 95 percent of the time, meaning the candidate biomarker was 95 percent sensitive.

In further analysis, the researchers demonstrated that the THOR was hypermethylated in tumors that went on to progress from low to high grade and that went on to become metastatic. According to Tabori, this suggests that preventing THOR hypermethylation might prevent cancer from progressing and that THOR hypermethylation may be a biomarker to predict which low-grade pediatric central cancers will become malignant.

Consistent with the latter idea, for the 45 samples from children with ependymomas, THOR hypermethylation predicted worse outcome. Patients with ependymomas with THOR hypermethylation had a five-year overall survival of 51 percent compared with 95 percent for patients with ependymomas without this hypermethylation.

"This is a DNA-based assay, which is simple to do in every lab in the world," Tabori said. "The tool is so sensitive and specific that you can actually detect before you can see it."

In the future, Tabori and colleagues hope to expand this research to common adult cancers such as gliomas and prostate and colon cancers, where the ability to predict which cancers will be more aggressive could have a large effect on patient care.

This study was funded by the Canadian Institute of Health Research and the Terry Fox Foundation. Tabori declares no conflicts of interest.

Explore further: Next-generation sequencing test identified potential targets for pediatric cancer treatments

More information:

Related Stories

Next-generation sequencing test identified potential targets for pediatric cancer treatments

November 5, 2013
A comprehensive genomic profiling test using next-generation sequencing has identified genomic alterations in more than half of pediatric cancer samples tested that would give clinicians potential targets on which to base ...

New mutations driving malignant melanoma discovered

January 24, 2013
Two new mutations that collectively occur in 71 percent of malignant melanoma tumors have been discovered in what scientists call the "dark matter" of the cancer genome, where cancer-related mutations haven't been previously ...

Immortality gene mutation identifies brain tumors, other cancers

March 18, 2013
Newly identified mutations in a gene that makes cells immortal appear to play a pivotal role in three of the most common types of brain tumors, as well as cancers of the liver, tongue and urinary tract, according to research ...

Three out of every four cases of bladder cancer display mutations in the same gene

September 10, 2013
Researchers from the Spanish National Cancer Research Centre (CNIO) have discovered that more than 70% of bladder tumours display somatic mutations in the TERT gene (telomerase reverse transcriptase). The TERT gene is involved ...

Scientists find mutation driving pediatric brain tumors

April 30, 2013
A type of low-grade but sometimes lethal brain tumor in children has been found in many cases to contain an unusual mutation that may help to classify, diagnose and guide the treatment of the tumors, report scientists at ...

Recommended for you

How a non-coding RNA encourages cancer growth and metastasis

August 21, 2017
A mechanism that pushes a certain gene to produce a non-coding form of RNA instead of its protein-coding alternative can promote the growth of cancer, report researchers at the Medical University of South Carolina (MUSC) ...

Spaser can detect, kill circulating tumor cells to prevent cancer metastases, study finds

August 21, 2017
A nanolaser known as the spaser can serve as a super-bright, water-soluble, biocompatible probe capable of finding metastasized cancer cells in the blood stream and then killing these cells, according to a new research study.

Comprehensive genomic analysis offers insights into causes of Wilms tumor development

August 21, 2017
A comprehensive genomic analysis of Wilms tumor - the most common kidney cancer in children - found genetic mutations involving a large number of genes that fall into two major categories. These categories involve cellular ...

Comparison of screening recommendations indicates annual mammography

August 21, 2017
When to initiate screening for breast cancer, how often to screen, and how long to screen are questions that continue to spark emotional debates. A new study compares the number of deaths that might be prevented as a result ...

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.