Work

Epco-03. a Comprehensive Single-cell Atlas of Schwannoma Reveals Conserved Cellular States Across Different Genetic Backgrounds and Anatomic Locations

Year: 2023

Type: article

Abstract: BACKGROUND Despite being associated with molecular alterations in the NF2 gene, there is limited understanding of the gene expression programs that govern the behavior of schwannomas both in sporadic cases as well as in patients with schwannoma predisposition syndromes, and also with respect to their anatomic location. METHODS We characterized the transcriptional heterogeneity of schwannomas across different genetic backgrounds and anatomic locations at the single-cell level. Tumor samples from patients undergoing resection for symptomatic schwannoma were dissociated and single cells were processed for full-transcript whole transcriptome profiling via Smart-seq2. Our cohort of 22 schwannomas, includes 5 tumors from schwannomatosis patients, 11 tumors from neurofibromatosis type 2 patients, and 6 sporadic tumors – 3 of which had grown after radiation treatment. Anatomically, 12 tumors were excised from cranial nerves (11 vestibular, 1 accessory) and 10 from spinal and other peripheral nerves. RESULTS We profiled 11,373 cells, including 4725 neoplastic cells, 2425 fibroblasts, 1314 T cells, 1258 endothelial cells, 969 myeloid cells, 503 pericytes and 240 Schwann cells. Copy number alteration analyses reveal evidence of intratumoral polyclonality (supporting the hypothesis of multiple sites of origin for a tumor). Using non-negative matrix factorization, we identify 6 distinct transcriptional metaprograms, with gene signatures related to stress, myelin production, antigen presentation, interferon signaling, glycolysis and extracellular matrix. After comparison with a pan-cancer gene expression dataset, we note unique interferon and antigen presentation metaprograms in schwannoma, with the latter being mainly characterized by expression of MHC Class II genes. Overall, we observe conserved expression of these metaprograms across anatomic locations and genetic backgrounds, with the exception of decreased interferon signaling for vestibular tumors. CONCLUSION We provide a comprehensive single-cell characterization of schwannoma spanning diverse genetic and anatomic backgrounds. We describe unique transcriptional metaprograms for antigen presentation and interferon signaling, which might underlie mechanisms for immune evasion.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/noad179.0468