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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>