Researchers identify genetic alterations that make a type of brain cancer more aggressive

September 7, 2017

Among the cancerous brain tumors, 70 percent are astrocytomas. Fatal in as many as 90 percent of cases, astrocytomas originate in the largest and most numerous cells in the central nervous system, called astrocytes because of their star shape.

A study conducted by biologist Valeria Valente, a researcher at São Paulo State University in Brazil, with support from the São Paulo Research Foundation (FAPESP), explores the mechanisms that make so aggressive and seeks ways to customize treatment to patient needs.

The study identified the genetic alterations with the most potential to promote aggressiveness, pointing to possible prognostic biomarkers and that could be candidate therapeutic targets. "We discovered a very strong correlation between alterations in the expression of astrocytoma cell repair genes and patient survival prognosis," Valente said.

The study focused on glioblastomas, the most aggressive of the four subtypes into which the World Health Organization (WHO) classifies astrocytomas. Patients with this type of survive 14 months on average.

"The point was to characterize the cellular alterations that promote the aggressive behavior of glioblastomas, tumors with a very high mortality rate. They're practically untreatable owing to their aggressiveness and their location in the brain," Valente explained. The study was published in Tumor Biology.

Valente and her team worked on astrocytoma cells collected from 55 patients submitted to surgical resection for tumor removal at the general hospital of the University of São Paulo's School of Medicine of Ribeirão Preto (FMRP-USP), looking for gene expression signatures associated with patient survival time.

The samples analyzed included cells from 42 glioblastomas (grade IV) and from 12 astrocytomas (six grade III and six grade II), which are still fatal but much less aggressive—patient survival can reach five years.

"In these comparisons, we found 19 genes with significantly altered expression. It was diminished in some genes, but in most cases, it was greatly augmented. Some genes were expressed as much as 100 times more highly in tumor tissue than healthy tissue," Valente said.

"We then defined gene expression signatures representing these alterations, in isolation and in all possible combinations, and investigated whether there was a correlation between the presence of the signature and patient survival."

The search was conducted using publicly available data from a much larger set of cases, giving the study statistical strength. Once they had detected the genetic signatures in the samples, they separated the into two groups according to the presence or absence of a specific signature.

The researchers found the average survival time for each group and identified signatures that correlated with shorter prognoses, establishing a methodology capable of predicting the aggressiveness of the disease based on the presence of each gene signature. "An alteration in just one gene could correlate with a worse prognosis," Valente said. "We developed a strategy to correlate gene signatures with tumor behavior. This can be used to predict patient prognosis and drive the development of novel therapies."

Until a cure is found for the most aggressive astrocytomas, the priority for oncologists is to detect their existence as early as possible so that treatment by surgery, radiation or chemotherapy can begin rapidly and patient survival can be prolonged.

Explore further: Deep, integrated genomic analysis re-classifies lower-grade brain tumors

More information: Juliana Ferreira de Sousa et al. Expression signatures of DNA repair genes correlate with survival prognosis of astrocytoma patients, Tumor Biology (2017). DOI: 10.1177/1010428317694552

Related Stories

Deep, integrated genomic analysis re-classifies lower-grade brain tumors

April 8, 2014
Comprehensive genomic analysis of low-grade brain tumors sorts them into three categories, one of which has the molecular hallmarks and shortened survival of glioblastoma multiforme, the most lethal of brain tumors, researchers ...

Single-cell RNA sequencing reveals detailed composition of two major types of brain tumor

March 30, 2017
Detailed analysis of two brain tumor subtypes has revealed that they may originate from the same type of neural progenitor cells and be distinguished by gene mutation patterns and by the composition of their microenvironments. ...

New way to identify brain tumor aggressiveness

January 28, 2016
A comprehensive analysis of the molecular characteristics of gliomas—the most common malignant brain tumor—explains why some patients diagnosed with slow-growing (low-grade) tumors quickly succumb to the disease while ...

Biomarkers for identifying tumor aggressiveness

July 26, 2017
Early-stage colon cancer patients could benefit in the future from specific genetic tests that forecast their prognosis and help them make the right decision regarding chemotherapy. Two of the biomarkers involved are the ...

Researchers identify enzyme involved in deadly brain tumors

January 17, 2013
One of the most common types of brain tumors in adults, glioblastoma multiforme, is one of the most devastating. Even with recent advances in surgery, radiation and chemotherapy, the aggressive and invasive tumors become ...

Study supports IDH gene as prognostic marker in anaplastic astrocytoma

June 3, 2015
New findings suggest that a gene called IDH1 might be prognostic marker for a rare form of brain cancer. Patients in this study who had a mutated IDH gene lived an average of 7.9 years after diagnosis versus 2.8 years for ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...

0 comments

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.