Somatic Genomic Defects And Tumor Progression In NF1-associated Tumors

Abstract Background: Neurofibromatosis type 1 (NF1) is a common inherited tumor predisposition syndrome. Many genetic and biochemical evidences considered NF1 gene as a tumor suppressor gene that inactivation of both NF1 alleles would lead to tumorigenesis. However, the clinical evaluation and early detection of malignant transformation from plexiform neurofibromas is often challenging. Methods: We used Affymetrix’s OncoScan FFPE Assay to record copy number gains and losses of common cancer genes in 24 NF1-associated tumors and compared with their NF1 mutation status. In addition, we carried out immunohistochemical studies of NF1, SUZ12 and H3K27me3 to evaluate gene expression in NF1-associated tumors to elucidate their potential roles during neurofibromatosis. Results: The most common Copy number alterations (CNAs) identified in this study were copy number loss (bi-allelic loss) of NF1 (N=8) and SUZ12 ( N =7). Many concurrent alterations of both NF1 and SUZ12 were also observed in these NF1-associated tumors. We found that the molecular events contributing to these tumors (both PNFs and MPNST) are very heterogeneous and not all MPNST harbour biallelic NF1 inactivation. We also observed some unexplained features need to be clarified in a set of NF1-associated tumors with the genetic results and NF1, SUZ12 and H3K27me3 proteins expression. Conclusions: We suggest that dividing NF1-associated tumors into subsets by the genetic spectrum of coordinate signaling pathway and tumor pathology may have practical implications for further choice of therapies.