Potentially disfiguring facial tumor caused by chromosomal chimera
This is the story of two perfectly harmless genes. By themselves, PAX3 and MAML3 don’t cause any problems. However, when they combine during an abnormal but recurring chromosomal mismatch, they can be dangerous. The result is a chimera — a gene that is half of each — and that causes biphenotypic sinonasal sarcoma. The tumor usually begins in the nose and may infiltrate the rest of the face, requiring disfiguring surgery to save the individual. Because Mayo Clinic pathology researchers have now described the molecular makeup of the rare tumor, several existing cancer drugs may be targeted against it. The findings appear in the current issue of Nature Genetics.
In 2004, Mayo Clinic pathologists Andre Oliveira, M.D., Ph.D., and Jean Lewis, M.D., first noticed something unusual about a tumor sample they were analyzing under the microscope. By 2009, they had seen the same pathology several times and had begun collecting data. In 2012, they and a team of Mayo collaborators published their discovery and defined a new class of tumor not previously described.
Now, less than two years later, they are informing the medical community of the “nature of the beast” — the genetic structure and molecular signature of this seldom-recognized type of cancer, which seems to strike women 75 percent of the time. It is rare, but how rare no one knows as most of the cases they examined were initially diagnosed as various other types of cancer. They were able to first identify and then characterize it because Mayo Clinic is considered one of the world’s largest referral centers for sarcoma diagnosis and treatment.
“It’s unusual that a condition or disease is recognized, subsequently studied in numerous patients, and then genetically characterized all at one place,” says Dr. Oliveira, who subspecializes in the molecular genetics of sarcomas. “Usually these things happen over a longer period of time and involve separate investigators and institutions. Because of Mayo’s network of experts, patient referrals, electronic records, bio repositories, and research scientists, it all happened here. And this is only the tip of the iceberg. Who knows what is in our repositories waiting to be discovered.”
First Seen Nearly 60 Years Earlier
While the cancer wasn’t formally identified until 2009, a subsequent search of Mayo Clinic’s medical records showed that a Mayo patient had the cancer in 1956. The identical description was found in physician notes within Mayo’s computerized database and confirmed with careful microscopic analysis. Dr. Oliveira took his investigation one step further and located that patient’s original tumor samples kept all those years in Mayo’s bio repositories. His analysis confirmed that the tumor possessed this same genetic chimera. In a way, Mayo Clinic had discovered the same rare cancer twice. The notes from the original physician added to the findings of the more recent discovery. For Dr. Oliveira, it was a surprising but not unheard of “collaboration” with a Mayo colleague from two generations ago.
Significance of the Discovery
Other than the increased knowledge about this rare cancer, its mechanisms and the potential for a treatment drug, researchers also are interested in the discovery because of its potential as a disease model.
“The PAX3-MAML3 chimera we identified in this cancer has some similarities to a unique protein found in alveolar rhabdomyosarcoma, a common cancer found in children,” says Mayo Clinic molecular biologist and co-author Jennifer Westendorf, Ph.D. “Our findings may also lead to a better understanding of this pediatric disease for which, unfortunately, there is no specific treatment.”
The research was supported by Mayo Clinic and the National Institutes of Health. Other co-authors include Xiaoke Wang; Krista Bledsoe; Rondell Graham, M.B.B.S.; Yan Asmann, Ph.D.; David Viswanatha, M.D.; Jean Lewis, M.D.; Jason Lewis, M.D.; Margaret Chou, Ph.D.; Michael Yaszemski, M.D., Ph.D.; and Jin Jen, M.D., Ph.D., all of Mayo Clinic.
About Mayo Clinic
Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit 150years.mayoclinic.org, http://www.mayoclinic.org and newsnetwork.mayoclinic.org.
About Mayo Clinic Cancer Center
As a leading institution funded by the National Cancer Institute, Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call 507-538-7623.
Robert Nellis, Mayo Clinic Public Affairs, 507-284-5005, firstname.lastname@example.org
Robert Nellis | Eurek Alert!
New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute
X-ray experiments reveal two different types of water
27.06.2017 | Deutsches Elektronen-Synchrotron DESY
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
27.06.2017 | Earth Sciences
27.06.2017 | Earth Sciences
27.06.2017 | Life Sciences