A clinically and genomically annotated nerve sheath tumor biospecimen repository

Abstract

Nerve sheath tumors occur as a heterogeneous group of neoplasms in patients with neurofibromatosis type 1 (NF1). The malignant form represents the most common cause of death in people with NF1, and even when benign, these tumors can result in significant disfigurement, neurologic dysfunction, and a range of profound symptoms. Lack of human tissue across the peripheral nerve tumors common in NF1 has been a major limitation in the development of new therapies. To address this unmet need, we have created an annotated collection of patient tumor samples, patient-derived cell lines, and patient-derived xenografts, and carried out high-throughput genomic and transcriptomic characterization to serve as a resource for further biologic and preclinical therapeutic studies. In this work, we release genomic and transcriptomic datasets comprised of 55 tumor samples derived from 23 individuals, complete with clinical annotation. All data are publicly available through the NF Data Portal and at

Integrative Analysis Identifies Candidate Tumor Microenvironment and Intracellular Signaling Pathways that Define Tumor Heterogeneity in NF1

“…Links to specific datasets and the access teams required to download them can be found using Synapse ID syn21221980. Genomic variant data were collected from exome-Seq [37] or whole-genome sequencing [38]. Variant call format (VCF) files were processed using "vcf2maf" (https://github.com/mskcc/vcf2maf) according to the workflow located at https://github.com/Sage-Bionetworks/rare-disease-workflows/ tree/master/gene-variant-workflow and then uploaded to the NF Data Portal.…”

“…To measure the diversity of the nerve sheath tumors at the transcriptomic level, we re-processed RNA-seq data from three published datasets [37][38][39] and one unpublished dataset. Despite having four types of nerve sheath tumors (cNFs, pNFs, NFs, and MPNSTs) across four datasets, we observed confounding batch effects ( Figure 1A) as some tumor types (e.g., cNF and NF) were derived from separate studies.…”

Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1

“…To measure the diversity of the nerve sheath tumors at the transcriptomic level, we re-processed RNA-seq data from three published datasets [33][34][35] and one unpublished dataset. Despite having four types of nerve sheath tumors (cNFs, pNFs, NFs and MPNSTs) across four datasets, we observed confounding batch effects ( Figure 1A) as some tumor types (eg.…”

“…Links to specific datasets and the access teams required to download them can be found using Synapse ID syn21221980 . Genomic variant data was collected from exome-Seq [35] or whole-genome sequencing [33] . VCFs were processed via vcf2maf ( https://github.com/mskcc/vcf2maf ) according to the workflow located at https://github.com/Sage-Bionetworks/rare-disease-workflows/tree/master/gene-variant-workflow and then uploaded to the NF Data Portal.…”

Distinctive Epigenomic Alterations in NF1-deficient Cutaneous and Plexiform Neurofibromas Drive Differential MKK/p38 Signaling

“…In order to con rm whether CNFs and PNFs are genomically and transcriptomically distinct lesions using advanced sequencing techniques, we compared publicly available RNAseq data from an NF1 test cohort where cutaneous/non-plexiform neuro bromas were compared to PNFs 16 . Principal Component Analysis (PCA) of the RNA-seq data con rmed that histologically identical cutaneous CNFs and PNFs cannot be discriminated based on global gene expression pro les, largely due to transcript heterogeneity (Fig.…”