Genetics & Genomics of Cancer

While loss of NF1 gene expression and function is absolutely required for NF1-associated brain and nerve tumor formation, we have recently identified additional cooperating genetic changes that influence glioma and nerve sheath tumor growth. Leveraging whole genome and exome sequencing coupled with epigenetic strategies, we are interested in defining the genomic and genetic landscape of these tumors as an initial step toward developing the most authentic preclinical mouse models in the laboratory and designing more optimized treatments for clinical use.

Current projects in the Gutmann research laboratory are focused on DNA-based sequencing of human low-grade brainstem gliomas and neurofibromas to identify actionable mutations and epigenetic changes. We are also coupling these approaches with microglia and macrophage RNA sequencing to discover stromal factors that dictate glioma growth.

Genetics&Genomics

Genetics&Genomics2

Genes mutated in the MPNST validation set (A). A schematic representation of the βIII-spectrin protein with the location of the missense mutations denoted (B). Positive βIII-spectrin immunostaining was not found in neurofibromas (C), schwannomas (D), or normal peripheral nerve (E), but was observed in the majority of MPNSTs with SPTBN2 mutations (F) as well as in MPNSTs without SPTBN2 mutations (G). H, normal cerebellum was included as an internal control for positive βIII-spectrin immunostaining.

Genes mutated in the MPNST validation set (A). A schematic representation of the βIII-spectrin protein with the location of the missense mutations denoted (B). Positive βIII-spectrin immunostaining was not found in neurofibromas (C), schwannomas (D), or normal peripheral nerve (E), but was observed in the majority of MPNSTs with SPTBN2 mutations (F) as well as in MPNSTs without SPTBN2 mutations (G). H, normal cerebellum was included as an internal control for positive βIII-spectrin immunostaining.