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 Why do animals fight members of other species?
24.04.2015 | University of California - Los Angeles

nachricht Is a small artificially composed virus fragment the key to a Chikungunya vaccine?
24.04.2015 | Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Im Focus: NOAA, Tulane identify second possible specimen of 'pocket shark' ever found

Pocket sharks are among the world's rarest finds

A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...

Im Focus: Drexel materials scientists putting a new spin on computing memory

Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.

Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...

Im Focus: Exploding stars help to understand thunderclouds on Earth

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...

Im Focus: On the trail of a trace gas

Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.

In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

 
Latest News

Electrons Move Like Light in Three-Dimensional Solid

24.04.2015 | Materials Sciences

Connecting Three Atomic Layers Puts Semiconducting Science on Its Edge

24.04.2015 | Materials Sciences

Understanding the Body’s Response to Worms and Allergies

24.04.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>