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 Pathogenic bacteria hitchhiking to North and Baltic Seas?
22.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Unconventional quasiparticles predicted in conventional crystals
22.07.2016 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

Im Focus: A Peek into the “Birthing Room” of Ribosomes

Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis

A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...

Im Focus: New protocol enables analysis of metabolic products from fixed tissues

Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.

In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...

Im Focus: Computer Simulation Renders Transient Chemical Structures Visible

Chemists at the University of Basel have succeeded in using computer simulations to elucidate transient structures in proteins. In the journal Angewandte Chemie, the researchers set out how computer simulations of details at the atomic level can be used to understand proteins’ modes of action.

Using computational chemistry, it is possible to characterize the motion of individual atoms of a molecule. Today, the latest simulation techniques allow...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

Hey robot, shimmy like a centipede

22.07.2016 | Information Technology

New record in materials research: 1 terapascals in a laboratory

22.07.2016 | Physics and Astronomy

University of Graz researchers challenge 140-year-old paradigm of lichen symbiosis

22.07.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>