Dr. Angela Hirbe led a multi-investigator research effort to generate a large collection of patient-derived tumor lines from NF1 patients with the most deadly NF1-associated cancer – malignant peripheral nerve sheath tumors (MPNSTs). These human cancer lines were developed from actual human tumors in order to identify the genetic changes that cause these tumors.
This exciting work has been part of a longstanding collaboration with scientists at Johns Hopkins University (JHU) and the National Cancer Institute (NCI). Dr. Carina Dehner, a pathology fellow at Washington University, James Moon and Andy Zhou, two biostatistics masters students at Washington University, and Dr. Xiyuan Zhang, a postdoctoral fellow at the NCI have worked closely on this project.
Together, this team comprehensively characterized the genomics of MPNST, and discovered that all MPNSTs gain at least one extra copy of part of chromosome 8. Additionally, they found that gain of chromosome 8 was associated with poor survival in other cancers, which may explain why MPNST are so aggressive.
The team is now actively working to determine which genes on chromosome 8 are critical for cancer formation and to use that information to develop new therapies for MPNST.
This landmark study was funded by the Neurofibromatosis Therapeutic Acceleration Program (NTAP) the Neurofibromatosis Research Initiative (NFRI) and the St. Louis Men’s Group Against Cancer, and was recently published in JCI Insight.
Dehner C, Moon CI, Zhang X, Zhou Z, Miller C, Xu H, Wan X, Yang K, Mashl J, Gosline SJ, Wang Y, Zhang X, Godec A, Jones PA, Dahiya S, Bhatia H, Primeau T, Li S, Pollard K, Rodriguez FJ, Ding L, Pratilas CA, Shern JF, Hirbe AC. Chromosome 8 gain is associated with high-grade transformation in MPNST. JCI Insight. 2021 Mar 22;6(6):e146351. doi: 10.1172/jci.insight.146351. PMID: 33591953