Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients
Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the cha...
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| Veröffentlicht in: | Blood cancer journal (New York) 2020-02, Vol.10 (2), p.14-14, Article 14 |
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| creator | Medina, Alejandro Jiménez, Cristina Sarasquete, M. Eugenia González, Marcos Chillón, M. Carmen Balanzategui, Ana Prieto-Conde, Isabel García-Álvarez, María Puig, Noemí González-Calle, Verónica Alcoceba, Miguel Cuenca, Isabel Barrio, Santiago Escalante, Fernando Gutiérrez, Norma C. Gironella, Mercedes Hernández, Miguel T. Sureda, Anna Oriol, Albert Bladé, Joan Lahuerta, Juan-José San Miguel, Jesús F. Mateos, María-Victoria Martínez-López, Joaquín Calasanz, María-José García-Sanz, Ramón |
| description | Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of
IGHV3
,
IGHD2
and
IGHD3
, as well as
IGHJ4
gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of
IGHD2
and
IGHD3
groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using
IGHD2/IGHD3
groups (HR: 0.552, 95% CI: 0.361−0.845,
p
= 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618,
p
= 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers. |
| doi_str_mv | 10.1038/s41408-020-0283-8 |
| format | Article |
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IGHV3
,
IGHD2
and
IGHD3
, as well as
IGHJ4
gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of
IGHD2
and
IGHD3
groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using
IGHD2/IGHD3
groups (HR: 0.552, 95% CI: 0.361−0.845,
p
= 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618,
p
= 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.</description><identifier>ISSN: 2044-5385</identifier><identifier>EISSN: 2044-5385</identifier><identifier>DOI: 10.1038/s41408-020-0283-8</identifier><identifier>PMID: 32029700</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 45/77 ; 631/67/1990/804 ; 692/308/2056 ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Female ; Follow-Up Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Rearrangement ; Hematology ; Humans ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Variable Region - genetics ; Immunoglobulins ; Male ; Middle Aged ; Multigene Family ; Multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - immunology ; Multiple Myeloma - pathology ; Oncology ; Pathogenesis ; Prognosis</subject><ispartof>Blood cancer journal (New York), 2020-02, Vol.10 (2), p.14-14, Article 14</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-84732191ed4a712ddbf687be28f8229402225fe1ece901da3d84dbde2fe5f9fe3</citedby><cites>FETCH-LOGICAL-c470t-84732191ed4a712ddbf687be28f8229402225fe1ece901da3d84dbde2fe5f9fe3</cites><orcidid>0000-0002-0374-3008 ; 0000-0003-4120-2787 ; 0000-0002-2510-8355 ; 0000-0002-3819-4846 ; 0000-0003-2390-1218 ; 0000-0001-5609-2969</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/PMC7004993/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004993/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27926,27927,41122,42191,51578,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32029700$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Medina, Alejandro</creatorcontrib><creatorcontrib>Jiménez, Cristina</creatorcontrib><creatorcontrib>Sarasquete, M. Eugenia</creatorcontrib><creatorcontrib>González, Marcos</creatorcontrib><creatorcontrib>Chillón, M. Carmen</creatorcontrib><creatorcontrib>Balanzategui, Ana</creatorcontrib><creatorcontrib>Prieto-Conde, Isabel</creatorcontrib><creatorcontrib>García-Álvarez, María</creatorcontrib><creatorcontrib>Puig, Noemí</creatorcontrib><creatorcontrib>González-Calle, Verónica</creatorcontrib><creatorcontrib>Alcoceba, Miguel</creatorcontrib><creatorcontrib>Cuenca, Isabel</creatorcontrib><creatorcontrib>Barrio, Santiago</creatorcontrib><creatorcontrib>Escalante, Fernando</creatorcontrib><creatorcontrib>Gutiérrez, Norma C.</creatorcontrib><creatorcontrib>Gironella, Mercedes</creatorcontrib><creatorcontrib>Hernández, Miguel T.</creatorcontrib><creatorcontrib>Sureda, Anna</creatorcontrib><creatorcontrib>Oriol, Albert</creatorcontrib><creatorcontrib>Bladé, Joan</creatorcontrib><creatorcontrib>Lahuerta, Juan-José</creatorcontrib><creatorcontrib>San Miguel, Jesús F.</creatorcontrib><creatorcontrib>Mateos, María-Victoria</creatorcontrib><creatorcontrib>Martínez-López, Joaquín</creatorcontrib><creatorcontrib>Calasanz, María-José</creatorcontrib><creatorcontrib>García-Sanz, Ramón</creatorcontrib><title>Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients</title><title>Blood cancer journal (New York)</title><addtitle>Blood Cancer J</addtitle><addtitle>Blood Cancer J</addtitle><description>Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of
IGHV3
,
IGHD2
and
IGHD3
, as well as
IGHJ4
gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of
IGHD2
and
IGHD3
groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using
IGHD2/IGHD3
groups (HR: 0.552, 95% CI: 0.361−0.845,
p
= 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618,
p
= 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.</description><subject>45/23</subject><subject>45/77</subject><subject>631/67/1990/804</subject><subject>692/308/2056</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Rearrangement</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulins</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multigene Family</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - immunology</subject><subject>Multiple Myeloma - pathology</subject><subject>Oncology</subject><subject>Pathogenesis</subject><subject>Prognosis</subject><issn>2044-5385</issn><issn>2044-5385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1Uctu1TAQjRCIVqUfwAZZYsMm4FcSZ4OEKihIRWxgbTnJONfFsYOd3Or-Ax_NpLeUgoQly6OZM2fO-BTFc0ZfMyrUmyyZpKqknOJVolSPilNOpSwroarHD-KT4jzna4qnqlnL2qfFieCUtw2lp8XPz9FDv3qTyJyidd6FkURL3DStIY4-diumyA7M_lD2O4PxCAFIApOSCSNMEJZM1rAH5zMJcEPmuGDOGb8xjiHmxfVkMuk7pExsTGRa_eJmD2Q6gI-TIbNZ3EbzrHhijc9wfveeFd8-vP968bG8-nL56eLdVdnLhi6lko3guAkM0jSMD0Nna9V0wJVVnLeScs4rCwx6aCkbjBiUHLoBuIXKthbEWfH2yDuv3QRDj7OT8XpODmUedDRO_10JbqfHuNf4ZbJtBRK8uiNI8ccKedGTyz14bwLENWsuKl4LUdcb9OU_0Ou4poDr3aLQJNSIKHZE9SnmnMDei2FUb3bro90a7dab3Vphz4uHW9x3_DYXAfwIyFhCq9Kf0f9n_QVPyrqE</recordid><startdate>20200206</startdate><enddate>20200206</enddate><creator>Medina, Alejandro</creator><creator>Jiménez, Cristina</creator><creator>Sarasquete, M. 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Eugenia ; González, Marcos ; Chillón, M. Carmen ; Balanzategui, Ana ; Prieto-Conde, Isabel ; García-Álvarez, María ; Puig, Noemí ; González-Calle, Verónica ; Alcoceba, Miguel ; Cuenca, Isabel ; Barrio, Santiago ; Escalante, Fernando ; Gutiérrez, Norma C. ; Gironella, Mercedes ; Hernández, Miguel T. ; Sureda, Anna ; Oriol, Albert ; Bladé, Joan ; Lahuerta, Juan-José ; San Miguel, Jesús F. ; Mateos, María-Victoria ; Martínez-López, Joaquín ; Calasanz, María-José ; García-Sanz, Ramón</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-84732191ed4a712ddbf687be28f8229402225fe1ece901da3d84dbde2fe5f9fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>45/23</topic><topic>45/77</topic><topic>631/67/1990/804</topic><topic>692/308/2056</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Rearrangement</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunoglobulins</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multigene Family</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - immunology</topic><topic>Multiple Myeloma - pathology</topic><topic>Oncology</topic><topic>Pathogenesis</topic><topic>Prognosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Medina, Alejandro</creatorcontrib><creatorcontrib>Jiménez, Cristina</creatorcontrib><creatorcontrib>Sarasquete, M. 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Eugenia</au><au>González, Marcos</au><au>Chillón, M. Carmen</au><au>Balanzategui, Ana</au><au>Prieto-Conde, Isabel</au><au>García-Álvarez, María</au><au>Puig, Noemí</au><au>González-Calle, Verónica</au><au>Alcoceba, Miguel</au><au>Cuenca, Isabel</au><au>Barrio, Santiago</au><au>Escalante, Fernando</au><au>Gutiérrez, Norma C.</au><au>Gironella, Mercedes</au><au>Hernández, Miguel T.</au><au>Sureda, Anna</au><au>Oriol, Albert</au><au>Bladé, Joan</au><au>Lahuerta, Juan-José</au><au>San Miguel, Jesús F.</au><au>Mateos, María-Victoria</au><au>Martínez-López, Joaquín</au><au>Calasanz, María-José</au><au>García-Sanz, Ramón</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients</atitle><jtitle>Blood cancer journal (New York)</jtitle><stitle>Blood Cancer J</stitle><addtitle>Blood Cancer J</addtitle><date>2020-02-06</date><risdate>2020</risdate><volume>10</volume><issue>2</issue><spage>14</spage><epage>14</epage><pages>14-14</pages><artnum>14</artnum><issn>2044-5385</issn><eissn>2044-5385</eissn><abstract>Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of
IGHV3
,
IGHD2
and
IGHD3
, as well as
IGHJ4
gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of
IGHD2
and
IGHD3
groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using
IGHD2/IGHD3
groups (HR: 0.552, 95% CI: 0.361−0.845,
p
= 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618,
p
= 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32029700</pmid><doi>10.1038/s41408-020-0283-8</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0374-3008</orcidid><orcidid>https://orcid.org/0000-0003-4120-2787</orcidid><orcidid>https://orcid.org/0000-0002-2510-8355</orcidid><orcidid>https://orcid.org/0000-0002-3819-4846</orcidid><orcidid>https://orcid.org/0000-0003-2390-1218</orcidid><orcidid>https://orcid.org/0000-0001-5609-2969</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2044-5385 |
| ispartof | Blood cancer journal (New York), 2020-02, Vol.10 (2), p.14-14, Article 14 |
| issn | 2044-5385 2044-5385 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7004993 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Free; PubMed Central; Springer Nature OA/Free Journals |
| subjects | 45/23 45/77 631/67/1990/804 692/308/2056 Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Research Female Follow-Up Studies Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Rearrangement Hematology Humans Immunoglobulin Heavy Chains - genetics Immunoglobulin Variable Region - genetics Immunoglobulins Male Middle Aged Multigene Family Multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - immunology Multiple Myeloma - pathology Oncology Pathogenesis Prognosis |
| title | Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T07%3A45%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Molecular%20profiling%20of%20immunoglobulin%20heavy-chain%20gene%20rearrangements%20unveils%20new%20potential%20prognostic%20markers%20for%20multiple%20myeloma%20patients&rft.jtitle=Blood%20cancer%20journal%20(New%20York)&rft.au=Medina,%20Alejandro&rft.date=2020-02-06&rft.volume=10&rft.issue=2&rft.spage=14&rft.epage=14&rft.pages=14-14&rft.artnum=14&rft.issn=2044-5385&rft.eissn=2044-5385&rft_id=info:doi/10.1038/s41408-020-0283-8&rft_dat=%3Cproquest_pubme%3E2352633663%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2352044901&rft_id=info:pmid/32029700&rfr_iscdi=true |