Mayo Clinic researchers discover origins of rare sarcoma
Volume 3, Issue 4, 2014
The new findings may help lead the way to better treatment of invasive nasal tumors.
Andre M. Oliveira, M.D., Ph.D., and Jean E. Lewis, M.D.
By themselves, the genes PAX3 and MAML3 don't cause 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 lifesaving but disfiguring surgery.
Mayo Clinic pathology researchers have now described the molecular makeup of this rare tumor, opening up the possibility for several existing cancer drugs to be targeted against it. The findings were published in Nature Genetics.
The story of this dangerous gene combination actually began long ago — in fact, much longer ago than researchers today initially realized.
It was in 2004 that Mayo Clinic Cancer Center pathologists Andre M. Oliveira, M.D., Ph.D., and Jean E. 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, with a team of Mayo Clinic collaborators, Drs. Oliveira and Lewis 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 genetic structure and molecular signature of biphenotypic sinonasal sarcoma, a malignant tumor found more commonly in women than in men.
As it turns out, Mayo Clinic actually uncovered this cancer decades ago. After the 2009 findings, Dr. Oliveira searched through years of computerized patient medical records to see if there was more information to be gleaned about biphenotypic sinonasal sarcoma. He was surprised to find physician notes on a patient from 1956 that described a virtually identical but unnamed tumor.
Dr. Oliveira was able to locate the patient's original tumor samples, which had been stored all those years in a Mayo Clinic biorepository. His analysis of the samples confirmed that the tumor had the same genetic chimera — it was biphenotypic sinonasal sarcoma.
The researchers were able to identify and characterize the tumor because Mayo Clinic is 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," said 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, biorepositories, and research scientists, it all happened here."
Watch a video of Dr. Oliveira and Jennifer Jane (Jennifer) Westendorf, Ph.D. discussing this study.