In 2012, a new type of cancer - causing facial tumors and primarily affecting women - was described. This cancer, known as biphenotypic sinonasal sarcoma (SNS), affects the nasal and paranasal pathway of middle-aged patients, and is quite rare. The tumor begins in the nose and can infiltrate the rest of the face, requiring disfiguring surgery to save the affected patient. The researchers who discovered this cancer, led by Drs. André Oliveira and Jean Lewis of the Mayo Clinic, have now identified the genetic makeup of this cancer.
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| chromosomal fusion of PAX3 and MAML3 |
Cytogenetic analysis has found that SNS is caused by a fusion, or chimera, of PAX3 and MAML3, genes that are harmless on their own. When combined during an abnormal but recurrent chromosomal mismatch, they result in a chimera - a new gene containing half of the two original genes. The PAX3-MAML3 fusion encodes a protein that is a potent transcriptional activator of PAX3 response elements. PAX3 is involved in ear, eye, and facial development; PAX3 mutations are associated with a number of human disorders, including Waardenburg syndrome and craniofacial-deafness-hand syndrome. MAML3 is a transcription activator for the NOTCH family of proteins, which are involved in cell proliferation, differentiation, and death.
The PAX3-MAML3 chimera altered the expression of several genes involved in neural crest, skeletal, and general embryonic development, particularly neurogenic genes like NTRK3, which is important in oncogenesis (the creation of cancer). The PAX3-MAML3 fusion closely resembles the activity of another PAX3 chimeric, PAX3-FOXO1, associated with Alveolar Rhabdomysarcoma, a common cancer in children.
The Mayo Clinic has released a video of the authors discussing SNS:
The authors are confident that this finding will help in the diagnosis and treatment of this rare cancer, and that it could also help researchers find better treatments for alveolar rhabdomysarcoma, for which there is currently no treatment.
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