Journal Article

A highly heterogeneous mutational pattern in POEMS syndrome

Zhang, Lu, Cai, Hao, Cao, Xin-xin, Chen, Jia, Gao, Xue-min, Zhou, Dao-bin, Zhao, Hao, Li, Jian

2021

Overview

POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. We analyzed the mutational features of purified bone marrow plasma cells from 42 patients newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes—LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)—and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/31 / 631/208/68 / 631/208/69 / 631/67/1990/2331 / Adult / Aged / Alleles / Amyloidosis / Biomarkers / Bone marrow / Bone Marrow - pathology / Bone Marrow Cells - metabolism / Bone Marrow Cells - pathology / Cancer Research / Care and treatment / Computational Biology - methods / Critical Care Medicine / Development and progression / Female / Gene expression / Gene mutations / Gene Ontology / Gene sequencing / Genes / Genetic aspects / Genetic Association Studies - methods / Genetic Heterogeneity / Genetic Predisposition to Disease / Genome-wide association studies / Genotype / Health aspects / Hematology / Humans / Intensive / Internal Medicine / Leukocytes (mononuclear) / Male / Medicine / Medicine & Public Health / Methods / Middle Aged / Multiple myeloma / Mutation / MyD88 protein / Oncology / Pathogenesis / Peripheral blood mononuclear cells / Plasma / Plasma cell diseases / Plasma cells / POEMS Syndrome - diagnosis / POEMS Syndrome - genetics / POEMS Syndrome - therapy / Polymorphism, Single Nucleotide / Ryanodine receptors / Stat3 protein / Syndecan-1 - genetics / Syndecan-1 - metabolism / Target recognition / USH2A protein / Whole Exome Sequencing