Genomic sequencing of 62-year-old patient leads to new treatment option
In a scientific first, the fusion of two genes, ALK and EML4, has been identified as the genetic driver in an aggressive type of thyroid cancer, according to a study by the Translational Genomics Research Institute (TGen).
These groundbreaking findings are based on genetic sequencing of tumor cells from a 62-year-old patient with an aggressive tall cell variant of papillary thyroid cancer, according to the study published Tuesday, March 18, in the World Journal of Surgery, the official journal of the International Society of Surgery.
The patient's thyroid cancer recurred after he had undergone multiple operations, external beam radiation and chemotherapy, and so the patient appeared to be a candidate for additional study.
Following one surgery in June 2011, a sample of the patient's tumor was obtained and studied by whole-genome sequencing, in which TGen spells out, in order, the more than 3 billion chemical base pairs that make up human DNA.
A comparison of the tumor DNA to the patient's normal DNA found 57 mutations in 55 genes of the cancer genome. The investigators also found a rearrangement between two genes. This translocation and fusion of EML4-ALK was identified as the genetic driver of the patient's cancer.
"This is the first report of the whole genome sequencing of a papillary thyroid cancer, in which we identified an EML4-ALK translocation. This is important because we have a drug that can target this fusion and treat the patient," said Dr. Michael J. Demeure, Clinical Professor and Director of TGen's Rare Cancer Unit, and the study's the study's principal investigator and lead author. "This patient's tumor did not harbor more well-known gene mutations that are associated with most thyroid cancers. These findings suggest that this tumor has a distinct oncogenesis, or the genetic cause of cancer."
There are few therapeutic options for patients with radioiodine-resistant aggressive papillary thyroid cancer. The EML4-ALK fusion appears in about 5 percent of lung cancers, which are usually treated with a targeted drug known as crizotinib.
By identifying the EML4-ALK fusion in this study, TGen was able to recommend crizotinib for this study's 62-year-old patient, whose cancer then remained progression-free for more than 6 months.
"Whole-genome sequencing technologies offer the promise of allowing for precision targeted treatment for human diseases, including cancer," said Dr. John Carpten, TGen Deputy Director of Basic Science, and Director of TGen's Integrated Cancer Genomics Division, and the study's senior author. "Through a greater understanding of the molecular oncogenesis of a specific cancer, one would hope to devise more effective, individualized treatments."
Whole genome sequencing is particularly beneficial for patients with relatively rare tumors, since they generally have less access to new drug treatments often available through clinical trials, according to the study, Whole-genome sequencing of an aggressive BRAF wild-type papillary thyroid cancer identified EML4-ALK translocation as a therapeutic target.
Also contributing to this study were physicians from Arizona Oncology, and Scottsdale Pathology Consultants.
# # #
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with cancer, neurological disorders and diabetes, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.
TGen Senior Science Writer
Steve Yozwiak | EurekAlert!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
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
18.07.2018 | Materials Sciences
18.07.2018 | Life Sciences
18.07.2018 | Health and Medicine