News Story

Researchers Use Whole Genome Sequencing to Identify Genes Involved in Malignant Peripheral Nerve Sheath Tumor Formation in NF1

Supplental Fig S1
Malignant peripheral never sheath tumors (MPNSTs) are extremely aggressive soft tissue sarcomas that occur more frequently in people with the Neurofibromatosis 1 (NF1) tumor predisposition syndrome.  These cancers often arise from benign plexiform neurofibromas.
Over the last several years, since completion of the sequencing of the human genome, whole genome sequencing techniques have become an important tool to understand the genetic changes that occur in cancer.
Leveraging these whole genome sequencing methods, Angela C. Hirbe, MD, PhD, an oncology fellow and postdoctoral researcher in Dr. David Gutmann’s laboratory has performed the first-ever whole exome sequencing to identify the genetic changes that accompany the transition from benign to malignant peripheral nerve sheath tumor in a single individual with NF1 over a 14-year period.
In these studies, Dr. Hirbe discovered a new gene which is both mutated and overexpressed in MPNSTs. Importantly, she found that reducing the levels of this protein in mouse MPNST cells decreased tumor growth. Dr. Hirbe is now working to determine how this new gene controls cancer cell growth relevant to the identification of new therapies for these deadly malignancies.
Hirbe AC, Dahiya S, Miller CA, Li T, Fulton RS, Zhang X, McDonald S, DeSchryver K, Duncavage EJ, Walrath J, Reilly KM, Abel HJ, Pekmezci M, Perry A, Ley TJ, Gutmann DH. Whole exome sequencing reveals the order of genetic changes during malignant transformation and metastasis in a single patient with NF1-plexiform neurofibroma. Clinical Cancer Research. 2015 Apr 29. Epub ahead of print.