Genetic and transcriptional landscape of plasma cells in POEMS syndrome

POEMS syndrome is a rare paraneoplastic disease, associated with monoclonal plasma cells whose pathogenic importance remains unclear. We performed comprehensive genetic analyses of plasma cells in 20 patients with POEMS syndrome. Whole exome sequencing and targeted sequencing identified 7 recurrently mutated genes: KLHL6, LTB, EHD1, EML4, HEPHL1, HIPK1, and PCDH10. None of the driver gene mutations frequently found in multiple myeloma (MM) such as NRAS, KRAS, BRAF, and TP53 was detected. Copy number analysis showed chromosomal abnormalities shared with monoclonal gammopathy of undetermined significance (MGUS). RNA sequencing revealed a transcription profile specific to POEMS syndrome, especially in terms of tumorigenesis. Unexpectedly, disease-specific VEGFA expression was not increased in POEMS syndrome. Our study illustrates that the genetic and transcriptional profiles of plasma cells in POEMS syndrome are distinct from MM and MGUS, indicating its unique pathogenesis.

• Type: Transcriptome Sequencing
• Archiver: Japanese Genotype-phenotype Archive (JGA)