Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia
Summary CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4...
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| Veröffentlicht in: | British journal of haematology 2021-08, Vol.194 (4), p.730-733 |
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| container_title | British journal of haematology |
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| creator | Gustine, Joshua N. Xu, Lian Yang, Guang Liu, Xia Kofides, Amanda Tsakmaklis, Nicholas Munshi, Manit Demos, Maria Guerrera, Maria L. Meid, Kirsten Patterson, Christopher J. Sarosiek, Shayna Branagan, Andrew R. Hunter, Zachary R. Castillo, Jorge J. Treon, Steven P. |
| description | Summary
CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant: targeted next‐generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele‐specific polymerase chain reaction (AS‐PCR) and Sanger sequencing with unselected and CD19‐selected BM samples. Our findings showed that targeted NGS frequently yielded false‐negative results. Both CD19 selection and AS‐PCR markedly improved detection of CXCR4S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality. |
| doi_str_mv | 10.1111/bjh.17385 |
| format | Article |
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CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant: targeted next‐generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele‐specific polymerase chain reaction (AS‐PCR) and Sanger sequencing with unselected and CD19‐selected BM samples. Our findings showed that targeted NGS frequently yielded false‐negative results. Both CD19 selection and AS‐PCR markedly improved detection of CXCR4S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.17385</identifier><identifier>PMID: 33713429</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Bone marrow ; Bone Marrow - metabolism ; Bone Marrow - pathology ; CD19 antigen ; Clinical trials ; CXCR4 ; CXCR4 protein ; Hematology ; High-Throughput Nucleotide Sequencing ; Humans ; ibrutinib ; Mutation ; next generation sequencing ; Point Mutation ; Polymerase chain reaction ; Receptors, CXCR4 - genetics ; Waldenstrom Macroglobulinemia - genetics ; Waldenstrom Macroglobulinemia - pathology ; Waldenström macroglobulinemia ; zanubrutinib</subject><ispartof>British journal of haematology, 2021-08, Vol.194 (4), p.730-733</ispartof><rights>2021 British Society for Haematology and John Wiley & Sons Ltd</rights><rights>2021 British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3885-9da43983bf3ad829073bf5dd2cb17415e2c5848175588c8135713b8d1028c043</citedby><cites>FETCH-LOGICAL-c3885-9da43983bf3ad829073bf5dd2cb17415e2c5848175588c8135713b8d1028c043</cites><orcidid>0000-0001-6717-7669 ; 0000-0001-6393-6154 ; 0000-0002-1689-1691</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjh.17385$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjh.17385$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33713429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gustine, Joshua N.</creatorcontrib><creatorcontrib>Xu, Lian</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Liu, Xia</creatorcontrib><creatorcontrib>Kofides, Amanda</creatorcontrib><creatorcontrib>Tsakmaklis, Nicholas</creatorcontrib><creatorcontrib>Munshi, Manit</creatorcontrib><creatorcontrib>Demos, Maria</creatorcontrib><creatorcontrib>Guerrera, Maria L.</creatorcontrib><creatorcontrib>Meid, Kirsten</creatorcontrib><creatorcontrib>Patterson, Christopher J.</creatorcontrib><creatorcontrib>Sarosiek, Shayna</creatorcontrib><creatorcontrib>Branagan, Andrew R.</creatorcontrib><creatorcontrib>Hunter, Zachary R.</creatorcontrib><creatorcontrib>Castillo, Jorge J.</creatorcontrib><creatorcontrib>Treon, Steven P.</creatorcontrib><title>Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant: targeted next‐generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele‐specific polymerase chain reaction (AS‐PCR) and Sanger sequencing with unselected and CD19‐selected BM samples. Our findings showed that targeted NGS frequently yielded false‐negative results. Both CD19 selection and AS‐PCR markedly improved detection of CXCR4S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.</description><subject>Bone marrow</subject><subject>Bone Marrow - metabolism</subject><subject>Bone Marrow - pathology</subject><subject>CD19 antigen</subject><subject>Clinical trials</subject><subject>CXCR4</subject><subject>CXCR4 protein</subject><subject>Hematology</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>ibrutinib</subject><subject>Mutation</subject><subject>next generation sequencing</subject><subject>Point Mutation</subject><subject>Polymerase chain reaction</subject><subject>Receptors, CXCR4 - genetics</subject><subject>Waldenstrom Macroglobulinemia - genetics</subject><subject>Waldenstrom Macroglobulinemia - pathology</subject><subject>Waldenström macroglobulinemia</subject><subject>zanubrutinib</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFuEzEUhi1ERUNhwQWQJTawmNZvPJ5xljQCCqqEhCrBbuSxX4Ijjx1sT0p2HIEjcIpeoDfhJLhNywKJt_FbfP79-_8JeQbsGMqcDOuvx9BxKR6QGfBWVDU08JDMGGNdBayRh-RxSmvGgDMBj8gh5x3wpp7PyK_T4JGOKsZwSa3fBrfFEX2myhuapkG74JWjxm4xJpt31I4bZWOiBjPqbIOnYUnHKauMhi6-LD41dNgVXq18SNlq6vF7_v3j5wo9RnV7IeG3Cb22flVepJ-VM-hTjtdXYzGiY1i5MEzOeoWjVU_IwVK5hE_vziNy8fbNxeKsOv_47v3i9XmluZSimhvV8Lnkw5IrI-s568oqjKn1AF0DAmstZCOhE0JKLYGLksAgDbBaatbwI_JyL7uJobhLuR9t0uic8him1NeCQd22kvGCvvgHXYcplpRuqBZaBkKKQr3aU-VDKUVc9ptoS867Hlh_01pfWutvWyvs8zvFaRjR_CXvayrAyR64tA53_1fqTz-c7SX_AIPipPI</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Gustine, Joshua N.</creator><creator>Xu, Lian</creator><creator>Yang, Guang</creator><creator>Liu, Xia</creator><creator>Kofides, Amanda</creator><creator>Tsakmaklis, Nicholas</creator><creator>Munshi, Manit</creator><creator>Demos, Maria</creator><creator>Guerrera, Maria L.</creator><creator>Meid, Kirsten</creator><creator>Patterson, Christopher J.</creator><creator>Sarosiek, Shayna</creator><creator>Branagan, Andrew R.</creator><creator>Hunter, Zachary R.</creator><creator>Castillo, Jorge J.</creator><creator>Treon, Steven P.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6717-7669</orcidid><orcidid>https://orcid.org/0000-0001-6393-6154</orcidid><orcidid>https://orcid.org/0000-0002-1689-1691</orcidid></search><sort><creationdate>202108</creationdate><title>Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia</title><author>Gustine, Joshua N. ; Xu, Lian ; Yang, Guang ; Liu, Xia ; Kofides, Amanda ; Tsakmaklis, Nicholas ; Munshi, Manit ; Demos, Maria ; Guerrera, Maria L. ; Meid, Kirsten ; Patterson, Christopher J. ; Sarosiek, Shayna ; Branagan, Andrew R. ; Hunter, Zachary R. ; Castillo, Jorge J. ; Treon, Steven P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3885-9da43983bf3ad829073bf5dd2cb17415e2c5848175588c8135713b8d1028c043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Bone marrow</topic><topic>Bone Marrow - metabolism</topic><topic>Bone Marrow - pathology</topic><topic>CD19 antigen</topic><topic>Clinical trials</topic><topic>CXCR4</topic><topic>CXCR4 protein</topic><topic>Hematology</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>ibrutinib</topic><topic>Mutation</topic><topic>next generation sequencing</topic><topic>Point Mutation</topic><topic>Polymerase chain reaction</topic><topic>Receptors, CXCR4 - genetics</topic><topic>Waldenstrom Macroglobulinemia - genetics</topic><topic>Waldenstrom Macroglobulinemia - pathology</topic><topic>Waldenström macroglobulinemia</topic><topic>zanubrutinib</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gustine, Joshua N.</creatorcontrib><creatorcontrib>Xu, Lian</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Liu, Xia</creatorcontrib><creatorcontrib>Kofides, Amanda</creatorcontrib><creatorcontrib>Tsakmaklis, Nicholas</creatorcontrib><creatorcontrib>Munshi, Manit</creatorcontrib><creatorcontrib>Demos, Maria</creatorcontrib><creatorcontrib>Guerrera, Maria L.</creatorcontrib><creatorcontrib>Meid, Kirsten</creatorcontrib><creatorcontrib>Patterson, Christopher J.</creatorcontrib><creatorcontrib>Sarosiek, Shayna</creatorcontrib><creatorcontrib>Branagan, Andrew R.</creatorcontrib><creatorcontrib>Hunter, Zachary R.</creatorcontrib><creatorcontrib>Castillo, Jorge J.</creatorcontrib><creatorcontrib>Treon, Steven P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gustine, Joshua N.</au><au>Xu, Lian</au><au>Yang, Guang</au><au>Liu, Xia</au><au>Kofides, Amanda</au><au>Tsakmaklis, Nicholas</au><au>Munshi, Manit</au><au>Demos, Maria</au><au>Guerrera, Maria L.</au><au>Meid, Kirsten</au><au>Patterson, Christopher J.</au><au>Sarosiek, Shayna</au><au>Branagan, Andrew R.</au><au>Hunter, Zachary R.</au><au>Castillo, Jorge J.</au><au>Treon, Steven P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>194</volume><issue>4</issue><spage>730</spage><epage>733</epage><pages>730-733</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant: targeted next‐generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele‐specific polymerase chain reaction (AS‐PCR) and Sanger sequencing with unselected and CD19‐selected BM samples. Our findings showed that targeted NGS frequently yielded false‐negative results. Both CD19 selection and AS‐PCR markedly improved detection of CXCR4S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>33713429</pmid><doi>10.1111/bjh.17385</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0001-6717-7669</orcidid><orcidid>https://orcid.org/0000-0001-6393-6154</orcidid><orcidid>https://orcid.org/0000-0002-1689-1691</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Bone marrow Bone Marrow - metabolism Bone Marrow - pathology CD19 antigen Clinical trials CXCR4 CXCR4 protein Hematology High-Throughput Nucleotide Sequencing Humans ibrutinib Mutation next generation sequencing Point Mutation Polymerase chain reaction Receptors, CXCR4 - genetics Waldenstrom Macroglobulinemia - genetics Waldenstrom Macroglobulinemia - pathology Waldenström macroglobulinemia zanubrutinib |
| title | Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia |
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