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 Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>