The first high-resolution analysis of genomic alterations in breast tumors is reported today in the scientific journal Genome Research. In this analysis, scientists from Cold Spring Harbor Laboratory, in collaboration with researchers from Scandinavia, identified three distinct patterns of genomic variation that underlie breast tumor formation, one of which--'firestorms'--may be predictive of aggressive disease progression and short survival.
"'Firestorms' are violent genomic disruptions that lead to destructive forms of breast cancer, even when the rest of the genome is relatively quiet," explains Dr. Jim Hicks, Senior Research Investigator at Cold Spring Harbor Laboratory and lead author on the paper.
Large-scale DNA alterations in cancer cells--rearrangements, deletions, and duplications--may assist in the proliferation and progression of the disease. "A thorough understanding of these changes will allow the design of more rational therapies," says Hicks. "Doctors will be able to recommend an appropriate course of treatment--hormonal therapy or chemotherapy--based on a patient's genomic profile."
Using a high-resolution genomic profiling technique called ROMA (Representational Oligonucleotide Microarray Analysis; see http://www.cshl.edu/public/releases/revealing.html), the scientists tested genomic DNA samples from 243 breast tumor samples acquired from the Karolinska Institute (Sweden) and the Oslo Micrometastasis Study (Norway). The samples were from patients whose clinical history had been documented, which allowed the scientists to associate the genomic profiles with clinical outcomes.
Most strikingly, Hicks and his co-workers found 'firestorms' of genomic amplification--tight chromosomal clusters where DNA segments had undergone multiple rounds of breakage, copying, and rejoining in a concerted manner. 'Firestorms' were found in 25% of the breast cancer samples and were associated with negative clinical outcomes. The amplifications were generally limited to single chromosomal arms and were flanked by broad segments of low-copy-number duplications and deletions.
Another complex genomic profile, called 'sawtooth,' was present in 5% of breast cancer samples. It was characterized by narrow, low-copy-number deletions and duplications that were evenly distributed across the chromosomes. The 'simplex' profile, affecting 60% of the tumor samples, exhibited broad genomic duplications and deletions that only affected a single chromosomal arm. The remaining 10% of the samples exhibited a 'flat' profile, reflecting normal levels of copy number variation in the genome (see http://www.cshl.edu/public/releases/genome.html).
In addition to potential clinical applications, the profiles described in this study will be useful for assessing the relationship between 'firestorms' and the locations of candidate oncogenes and tumor suppressors in the genome. It will assist the researchers in identifying genes that drive cancer progression, and help unravel the complex yet elusive genetic pathway that underlies tumor metastasis.
Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
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...
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...
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...
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....
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...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Earth Sciences
19.07.2018 | Power and Electrical Engineering
19.07.2018 | Materials Sciences