Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

09.04.2014

Three molecularly defined clusters could alter practice; 1 closely resembles deadly glioblastoma

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 reported at the American Association for Cancer Research Annual Meeting 2014.


This is Roel Verhaak, Ph.D.

Credit: MD Anderson Cancer Center

"The immediate clinical implication is that a group of patients with tumors previously categorized as lower grade should actually be treated as glioblastoma patients and receive that standard of care -- temozolomide chemotherapy and irradiation," said lead author Roel Verhaak, Ph.D. assistant professor of Bioinformatics and Computational Biology at The University of Texas MD Anderson Cancer Center.

"Classifying lower grade tumors in these three molecular clusters more accurately characterizes them than current methods used to group and grade tumors," Verhaak said.

The pivotal molecular markers that define the three tumor clusters – mutational status of the IDH1 and IDH2 genes and loss of chromosome arms 1p and 19q -- are already routinely checked in clinical care, Verhaak noted, so implementing the new categories can be done relatively quickly.

Verhaak and colleagues analyzed data from The Cancer Genome Atlas (TCGA) brain tumor studies.

Lack of IDH1/2 mutations drastically reduces survival

Brain tumors arise in the glia, or supportive cells, of the brain and now are classified by their histology – characteristics visible via microscopy – and their cell of origin, either astrocytes or oligodendrocytes.

Classified this way, grade 2 and 3 oligodendrogliomas and astrocytomas demonstrate median overall patient survival ranging from three to ten years. This compares with 14 months for patients with glioblastoma multiforme – a complex and aggressive astrocytoma.

Glioblastomas make up 55-60 percent of gliomas, with lower-grade astrocytomas comprising 15-20 percent of cases, oligodendrocytes 12-20 percent and combination oligo-astrocytomas at 5-10 percent.

The researchers comprehensively analyzed 254 TCGA lower-grade gliomas for gene, protein and micro RNA expression, DNA methylation and gene copy profiles to cluster cases by category. Then they conducted a "cluster of clusters" analysis that encompassed all data.

"The results overwhelmingly point to a natural grouping of lower-grade gliomas into three super clusters based on the mutational status of the IDH1 and IDH2 genes and co-deletion of chromosome arms 1p and 19q," Verhaak said.

Previous TCGA research had shown that glioblastoma patients with mutations of IDH1/IDH2 in their tumors have an improved prognosis. Verhaak said whether these mutations are markers of good prognosis or actually have a role in thwarting tumor progression is not known. Co-deletion of 1p19q has been associated with increased tumor sensitivity to chemotherapy and longer survival for oligodendroglioma patients.

Each molecular group includes tumors from all grades and categories of astrocytoma, oligodendrocytoma and oligo-astrocytoma

The three molecular super clusters of lower grade gliomas have either:

  • Wild-type IDHI1 and IDH2 with no mutations. These tumors are similar to glioblastoma, with patients' median survival at 18 months.
  • IDH1/IDH2 mutations and chromosome arms 1p/19q intact. No dominant histology or grade type, median survival of about seven years.
  • IDH1/IDH2 mutations and co-deletion of 1p/19q. This cluster was composed mainly of oligodendrogliomas (84 percent) and had median survival of about eight years.
###

Collaborators with Verhaak are Kenneth Aldape, M.D., of Pathology and W.K. Alfred Yung, M.D., of Neuro-Oncology at MD Anderson; Lee Cooper and Daniel Brat of Emory University, Atlanta; and Sofie Salama of the University of California Santa Cruz.

This research was funded by grants from the National Cancer Institute of the National Institutes of Health (U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U24CA143843, U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544, U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563, U24CA143731, U24CA143843.)

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

Further reports about: Cancer IDH1 IDH2 TCGA astrocytomas chemotherapy clusters genes genomic mutations oligodendrocytes prognosis tumors

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>