A highly heterogeneous mutational pattern in POEMS syndrome
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...
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| Veröffentlicht in: | Leukemia 2021-04, Vol.35 (4), p.1100-1107 |
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| description | 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. |
| doi_str_mv | 10.1038/s41375-020-01101-4 |
| format | Article |
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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.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-020-01101-4</identifier><identifier>PMID: 33262528</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><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</subject><ispartof>Leukemia, 2021-04, Vol.35 (4), p.1100-1107</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-571d1d3d4ee992caace6d271b1e30f42a88bd593e103f0e9bf14de105b3f2c5b3</citedby><cites>FETCH-LOGICAL-c473t-571d1d3d4ee992caace6d271b1e30f42a88bd593e103f0e9bf14de105b3f2c5b3</cites><orcidid>0000-0002-1592-1932 ; 0000-0002-4549-0694 ; 0000-0001-8032-060X ; 0000-0003-2153-9470 ; 0000-0003-3486-7705 ; 0000-0001-7884-3073</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-020-01101-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-020-01101-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33262528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Jia</creatorcontrib><creatorcontrib>Gao, Xue-min</creatorcontrib><creatorcontrib>Zhao, Hao</creatorcontrib><creatorcontrib>Cai, Hao</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Cao, Xin-xin</creatorcontrib><creatorcontrib>Zhou, Dao-bin</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><title>A highly heterogeneous mutational pattern in POEMS syndrome</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>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.</description><subject>13/31</subject><subject>631/208/68</subject><subject>631/208/69</subject><subject>631/67/1990/2331</subject><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Amyloidosis</subject><subject>Biomarkers</subject><subject>Bone marrow</subject><subject>Bone Marrow - pathology</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Bone Marrow Cells - pathology</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Computational Biology - methods</subject><subject>Critical Care Medicine</subject><subject>Development and progression</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene mutations</subject><subject>Gene Ontology</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies - 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pathology</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Bone Marrow Cells - pathology</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Computational Biology - methods</topic><topic>Critical Care Medicine</topic><topic>Development and progression</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene mutations</topic><topic>Gene Ontology</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies - methods</topic><topic>Genetic Heterogeneity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genotype</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukocytes (mononuclear)</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methods</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Mutation</topic><topic>MyD88 protein</topic><topic>Oncology</topic><topic>Pathogenesis</topic><topic>Peripheral blood mononuclear cells</topic><topic>Plasma</topic><topic>Plasma cell diseases</topic><topic>Plasma cells</topic><topic>POEMS Syndrome - diagnosis</topic><topic>POEMS Syndrome - genetics</topic><topic>POEMS Syndrome - therapy</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Ryanodine receptors</topic><topic>Stat3 protein</topic><topic>Syndecan-1 - genetics</topic><topic>Syndecan-1 - metabolism</topic><topic>Target recognition</topic><topic>USH2A protein</topic><topic>Whole Exome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Jia</creatorcontrib><creatorcontrib>Gao, Xue-min</creatorcontrib><creatorcontrib>Zhao, Hao</creatorcontrib><creatorcontrib>Cai, Hao</creatorcontrib><creatorcontrib>Zhang, Lu</creatorcontrib><creatorcontrib>Cao, Xin-xin</creatorcontrib><creatorcontrib>Zhou, Dao-bin</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Jia</au><au>Gao, Xue-min</au><au>Zhao, Hao</au><au>Cai, Hao</au><au>Zhang, Lu</au><au>Cao, Xin-xin</au><au>Zhou, Dao-bin</au><au>Li, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A highly heterogeneous mutational pattern in POEMS syndrome</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>35</volume><issue>4</issue><spage>1100</spage><epage>1107</epage><pages>1100-1107</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33262528</pmid><doi>10.1038/s41375-020-01101-4</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1592-1932</orcidid><orcidid>https://orcid.org/0000-0002-4549-0694</orcidid><orcidid>https://orcid.org/0000-0001-8032-060X</orcidid><orcidid>https://orcid.org/0000-0003-2153-9470</orcidid><orcidid>https://orcid.org/0000-0003-3486-7705</orcidid><orcidid>https://orcid.org/0000-0001-7884-3073</orcidid></addata></record> |
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| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2021-04, Vol.35 (4), p.1100-1107 |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | 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 |
| title | A highly heterogeneous mutational pattern in POEMS syndrome |
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