Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover new genetic subtypes of common blood cancer

11.04.2006
Varied gene signatures in multiple myeloma cells predict different outcomes, provide treatment targets

Scientists at Dana-Farber Cancer Institute and collaborators have identified four distinct genetic subtypes of multiple myeloma, a deadly blood cancer, that have different prognoses and might be treated most effectively with drugs specifically targeted to those subtypes.

A new computational tool based on an algorithm designed to recognize human faces plucked the four distinguishing gene patterns out of a landscape of many DNA alterations in the myeloma genome, the researchers report in the April issue of Cancer Cell.

These results "define new disease subgroups of multiple myeloma that can be correlated with different clinical outcomes," wrote the authors, led by Ronald DePinho, MD, director of Dana-Farber’s Center for Applied Cancer Science.

Not only do the findings pave the way for treatments tailored to a patient’s specific form of the disease, they also narrow down areas of the chromosomes in myeloma cells likely to contain undiscovered genetic flaws that drive myeloma, and which might turn out to be vulnerable to targeted designer drugs.

Kenneth Anderson, MD, medical director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber and an author of the paper, said the findings "allow us to predict how patients will respond to current treatments based on a genetic analysis of their disease." In addition, the findings "identify many new genes implicated in the cause and progression of myeloma, and the product of those genes can be targeted with novel therapies."

Multiple myeloma, the second most common blood cancer after non-Hodgkin’s lymphoma, is incurable, although some patients live for a number of years following diagnosis. About 50,000 people in the United States are living with the disease, and an estimated 16,000 new cases are diagnosed annually. Despite improvements in therapy, the five-year survival rate in multiple myeloma is only 32 percent and durable responses are rare.

The new report emerged from a collaboration involving DePinho’s Dana-Farber group, Cameron Brennan, MD, of Memorial Sloan-Kettering Cancer Center, and John Shaughnessy, MD, of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences. Lead authors are Daniel Carrasco, MD, PhD, and Giovanni Tonon, MD, PhD, of Dana-Farber, and Yongsheng Huang, MS, of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Science.

Myeloma cells’ genomes are scenes of rampant chaos: extra or missing chromosomes; pieces of broken chromosomes randomly reattached; genes that are mutated or amplified – present in too many copies – or are overexpressed or absent. The roles played by these myriad abnormalities in the initiation and progression of myeloma are only beginning to be understood, but it’s been observed that different abnormalities are often found from one patient to the next.

Previously, scientists had identified two genetic subtypes of myeloma. One, called hyperdiploid MM, is characterized by extra copies of entire chromosomes, and patients with this subtype appear to fare better. The non-hyperdiploid form lacks these extra chromosomes and instead has abnormal rearrangements between different chromosomes, and the outlook is generally worse for these patients.

The collaborating researchers sought to cast a wide net to capture as many of the genetic flaws in myeloma cells as possible, creating a comprehensive atlas of this cancerous genome. First, they used a technique called high-resolution array CGH (comparative genomic hybridization) to analyze samples from 67 newly diagnosed patients provided by Shaughnessy in Arkansas. The CGH technique compared the genomes of a normal blood cell with various myeloma cells in search of differences. The goal was to identify recurrent copy number alterations – hotspots on the chromosomes where genes were abnormally duplicated or lost across many different tumors.

The CGH analysis netted a large number of areas showing such alterations in the myeloma cells from patients. Then the scientists asked whether any specific pattern or combination of these aberrations in an individual patient might help predict how aggressive the disease would be.

For this deeper analysis, the researchers created an algorithm based on a recently developed computational method designed to recognize individuals by facial features. It is called non-negative matrix factorization, or NMF. In the myeloma study, the algorithm was used to group the results in a way that yielded distinctive genomic features from the CGH data.

Four distinct myeloma subtypes based on genetic patterns emerged: Two of them corresponded to the non-hyperdiploid and hyperdiploid types, and the latter was found to contain two further subdivisions, called k1 and k2 When these subgroups were checked against the records of the patients from whom the samples were taken, it showed that those with the k1 pattern had a longer survival than those with k2. Digging still deeper, the scientists found evidence suggesting that certain molecular signatures within the subgroups are responsible for the differences in outcomes, providing a clear and productive path for further research.

This narrowing down of potential genes and proteins within the subgroups "is a huge advance," comments DePinho. "If you know that a certain gene is driving the disease and influences the clinical behavior of the disease in humans, it immediately goes to the top of the list as a prime candidate for drug development."

Bill Schaller | EurekAlert!
Further information:
http://www.danafarber.org

More articles from Life Sciences:

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>