Young adults with Neurofibromatosis type 1 (NF1) are at risk for developing a rare type of sarcoma called a malignant peripheral nerve sheath tumor (MPNST). Unfortunately even with aggressive surgery, radiation, and chemotherapy, these cancers typically recur or spread to other parts of the body, and most patients with die within five years.
In an effort to discover new genetic mutations in these deadly sarcomas, Dr. Angela Hirbe and her colleagues at the Washington University NF Center employed a sequencing platform currently available to most cancer patients. This screening platform was designed to detect mutations in genes that can be targeted by novel drug compounds.
Dr. Hirbe found that one-third of these tumors harbored a mutation in the TYK2 gene, such that the protein made by this gene is increased in 60% of MPNSTs examined. The TYK2 protein is important for the growth and survival of cancer cells. In addition, there are drugs in development that can block the function of TYK2.
Ongoing work in Dr. Hirbe’s laboratory is focused on determining whether TYK2 expression identifies a subgroup of MPNSTs most likely to respond to this class of drugs.
This study was published in the journal, Cancer.
Hirbe AC, Kaushal M, Sharma MK, Dahiya S, Pekmezci M, Perry A, Gutmann DH. Clinical genomic profiling identifies TYK2 mutation and overexpression in patients with neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Cancer. 2017 Apr 1;123(7):1194-1201. doi: 10.1002/cncr.30455. Epub 2016 Nov 22. PMID: 27875628