Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing
Introduction We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time. Method...
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| description | Introduction We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time. Methods Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets. Results Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies. Conclusion NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease. |
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Methods Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets. Results Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies. Conclusion NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0253541</identifier><identifier>PMID: 34166440</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Antigens ; B cells ; Biology and Life Sciences ; Bone marrow ; Cancer ; Chains ; Gene rearrangement ; Genes ; Genetic aspects ; Heavy chains ; Hospitals ; IGK gene ; Immunoglobulins ; Laboratories ; Lymphoid cells ; Medical schools ; Medicine ; Medicine and Health Sciences ; Minority & ethnic groups ; Multiple myeloma ; Next-generation sequencing ; People and Places ; Plasma cells ; Research and analysis methods ; Variables</subject><ispartof>PloS one, 2021-06, Vol.16 (6), p.e0253541-e0253541</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Kim et al 2021 Kim et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-61c41f4a1867444598f34a9b6a1a61857178b545b8e416c803a1853ddf08c823</citedby><cites>FETCH-LOGICAL-c669t-61c41f4a1867444598f34a9b6a1a61857178b545b8e416c803a1853ddf08c823</cites><orcidid>0000-0003-0433-8028</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224885/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224885/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids></links><search><creatorcontrib>Kim, Miyoung</creatorcontrib><creatorcontrib>Jeon, Kibum</creatorcontrib><creatorcontrib>Hutt, Kasey</creatorcontrib><creatorcontrib>Zlotnicki, Alyssa M</creatorcontrib><creatorcontrib>Kim, Hyo Jung</creatorcontrib><creatorcontrib>Lee, Jiwon</creatorcontrib><creatorcontrib>Kim, Han-Sung</creatorcontrib><creatorcontrib>Kang, Hee Jung</creatorcontrib><creatorcontrib>Lee, Young Kyung</creatorcontrib><title>Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing</title><title>PloS one</title><description>Introduction We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time. Methods Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets. Results Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies. Conclusion NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.</description><subject>Analysis</subject><subject>Antigens</subject><subject>B cells</subject><subject>Biology and Life Sciences</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Chains</subject><subject>Gene rearrangement</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Heavy chains</subject><subject>Hospitals</subject><subject>IGK gene</subject><subject>Immunoglobulins</subject><subject>Laboratories</subject><subject>Lymphoid cells</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Minority & ethnic groups</subject><subject>Multiple myeloma</subject><subject>Next-generation sequencing</subject><subject>People and 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gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing</title><author>Kim, Miyoung ; Jeon, Kibum ; Hutt, Kasey ; Zlotnicki, Alyssa M ; Kim, Hyo Jung ; Lee, Jiwon ; Kim, Han-Sung ; Kang, Hee Jung ; Lee, Young Kyung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-61c41f4a1867444598f34a9b6a1a61857178b545b8e416c803a1853ddf08c823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Antigens</topic><topic>B cells</topic><topic>Biology and Life Sciences</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Chains</topic><topic>Gene rearrangement</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Heavy chains</topic><topic>Hospitals</topic><topic>IGK gene</topic><topic>Immunoglobulins</topic><topic>Laboratories</topic><topic>Lymphoid cells</topic><topic>Medical schools</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Minority & ethnic groups</topic><topic>Multiple myeloma</topic><topic>Next-generation sequencing</topic><topic>People and Places</topic><topic>Plasma cells</topic><topic>Research and analysis methods</topic><topic>Variables</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Miyoung</creatorcontrib><creatorcontrib>Jeon, Kibum</creatorcontrib><creatorcontrib>Hutt, Kasey</creatorcontrib><creatorcontrib>Zlotnicki, Alyssa M</creatorcontrib><creatorcontrib>Kim, Hyo Jung</creatorcontrib><creatorcontrib>Lee, Jiwon</creatorcontrib><creatorcontrib>Kim, Han-Sung</creatorcontrib><creatorcontrib>Kang, Hee Jung</creatorcontrib><creatorcontrib>Lee, Young Kyung</creatorcontrib><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central 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Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Miyoung</au><au>Jeon, Kibum</au><au>Hutt, Kasey</au><au>Zlotnicki, Alyssa M</au><au>Kim, Hyo Jung</au><au>Lee, Jiwon</au><au>Kim, Han-Sung</au><au>Kang, Hee Jung</au><au>Lee, Young Kyung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing</atitle><jtitle>PloS one</jtitle><date>2021-06-24</date><risdate>2021</risdate><volume>16</volume><issue>6</issue><spage>e0253541</spage><epage>e0253541</epage><pages>e0253541-e0253541</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Introduction We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time. Methods Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets. Results Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies. Conclusion NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34166440</pmid><doi>10.1371/journal.pone.0253541</doi><tpages>e0253541</tpages><orcidid>https://orcid.org/0000-0003-0433-8028</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Antigens B cells Biology and Life Sciences Bone marrow Cancer Chains Gene rearrangement Genes Genetic aspects Heavy chains Hospitals IGK gene Immunoglobulins Laboratories Lymphoid cells Medical schools Medicine Medicine and Health Sciences Minority & ethnic groups Multiple myeloma Next-generation sequencing People and Places Plasma cells Research and analysis methods Variables |
| title | Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T03%3A01%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Immunoglobulin%20gene%20rearrangement%20in%20Koreans%20with%20multiple%20myeloma:%20Clonality%20assessment%20and%20repertoire%20analysis%20using%20next-generation%20sequencing&rft.jtitle=PloS%20one&rft.au=Kim,%20Miyoung&rft.date=2021-06-24&rft.volume=16&rft.issue=6&rft.spage=e0253541&rft.epage=e0253541&rft.pages=e0253541-e0253541&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0253541&rft_dat=%3Cgale_plos_%3EA666328530%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2544866857&rft_id=info:pmid/34166440&rft_galeid=A666328530&rft_doaj_id=oai_doaj_org_article_80888204ee10431d83c540911ac93584&rfr_iscdi=true |