Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biological and clinical features
Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course while others have an indolent behavior. We performed an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B cell rece...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2012-08, Vol.72 (20), p.5307-5316 |
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| creator | Navarro, Alba Clot, Guillem Royo, Cristina Jares, Pedro Hadzidimitriou, Anastasia Agathangelidis, Andreas Bikos, Vasilis Darzentas, Nikos Papadaki, Theodora Salaverria, Itziar Pinyol, Magda Puig, Xavier Palomero, Jara Vegliante, Maria Carmela Amador, Virgina Martinez-Trillos, Alejandra Stefancikova, Lenka Wiestner, Adrian Wilson, Wyndham Pott, Christiane Calasanz, Maria Jose Trim, Nicola Erber, Wendy Sander, Birgitta Ott, German Rosenwald, Andreas Colomer, Dolors Giné, Eva Siebert, Reiner Lopez-Guillermo, Armando Stamatopoulos, Kostas Beà, Sílvia Campo, Elías |
| description | Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course while others have an indolent behavior. We performed an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B cell receptors may identify different subsets of tumors. ‘Truly unmutated’ (100% identity)
IGHV
genes were found in 24% cases, 40% were ‘minimally/borderline mutated’ (99.9-97%), 19% ‘significantly mutated’ (96.9-95%) and 17% ‘hypermutated’ ( |
| doi_str_mv | 10.1158/0008-5472.CAN-12-1615 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmedcentral</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3763938</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_3763938</sourcerecordid><originalsourceid>FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_37639383</originalsourceid><addsrcrecordid>eNqljM1KxDAcxIMobv14BOH_Al2btmm7F0EW3fWgHhTxVtL0320kH6VJF_scvrBRRPDsaWb4zQwhFzRZUsqqyyRJqpjlZbpcXz_ENI1pQdkBiSjLqrjMc3ZIot_Ogpw49xYiowk7Jos0XVFWFklEPu6tQjEpPoKbGofege1Ac-MVgkClQM166K3m0GInDbbQzOB7hLvN9gX05LmX1nAFLrjJATctPD2-Ugr4PozoXKDQ8z1CK52XRnhopFV2J0UYfbWFkuY7dBgewuSMHHVcOTz_0VNydXvzvN7Gw9RobAUaP3JVD6PUfJxry2X9lxjZ1zu7r7OyyFZZlf374BMEgnfu</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biological and clinical features</title><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Navarro, Alba ; Clot, Guillem ; Royo, Cristina ; Jares, Pedro ; Hadzidimitriou, Anastasia ; Agathangelidis, Andreas ; Bikos, Vasilis ; Darzentas, Nikos ; Papadaki, Theodora ; Salaverria, Itziar ; Pinyol, Magda ; Puig, Xavier ; Palomero, Jara ; Vegliante, Maria Carmela ; Amador, Virgina ; Martinez-Trillos, Alejandra ; Stefancikova, Lenka ; Wiestner, Adrian ; Wilson, Wyndham ; Pott, Christiane ; Calasanz, Maria Jose ; Trim, Nicola ; Erber, Wendy ; Sander, Birgitta ; Ott, German ; Rosenwald, Andreas ; Colomer, Dolors ; Giné, Eva ; Siebert, Reiner ; Lopez-Guillermo, Armando ; Stamatopoulos, Kostas ; Beà, Sílvia ; Campo, Elías</creator><creatorcontrib>Navarro, Alba ; Clot, Guillem ; Royo, Cristina ; Jares, Pedro ; Hadzidimitriou, Anastasia ; Agathangelidis, Andreas ; Bikos, Vasilis ; Darzentas, Nikos ; Papadaki, Theodora ; Salaverria, Itziar ; Pinyol, Magda ; Puig, Xavier ; Palomero, Jara ; Vegliante, Maria Carmela ; Amador, Virgina ; Martinez-Trillos, Alejandra ; Stefancikova, Lenka ; Wiestner, Adrian ; Wilson, Wyndham ; Pott, Christiane ; Calasanz, Maria Jose ; Trim, Nicola ; Erber, Wendy ; Sander, Birgitta ; Ott, German ; Rosenwald, Andreas ; Colomer, Dolors ; Giné, Eva ; Siebert, Reiner ; Lopez-Guillermo, Armando ; Stamatopoulos, Kostas ; Beà, Sílvia ; Campo, Elías</creatorcontrib><description>Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course while others have an indolent behavior. We performed an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B cell receptors may identify different subsets of tumors. ‘Truly unmutated’ (100% identity)
IGHV
genes were found in 24% cases, 40% were ‘minimally/borderline mutated’ (99.9-97%), 19% ‘significantly mutated’ (96.9-95%) and 17% ‘hypermutated’ (<95%). Tumors with high (≥97%) or low (<97%) mutational load used different
IGHV
genes and their gene expression profiles were also different for several gene pathways. A gene set enrichment analysis showed that MCL with high and low
IGHV
mutations were enriched in memory and naïve B-cell signatures, respectively. Furthermore, the highly mutated tumors displayed less genomic complexity, were preferentially
SOX11
negative, and showed more frequently non-nodal disease. The best cut-off of germline identity of
IGHV
genes to predict survival was 3%. Patients with high and low mutational load had significant different outcome with 5-year overall survival of 59% and 40%, respectively (
P
=0.004). Nodal presentation and SOX11 expression also predicted for poor overall survival. In a multivariate analysis,
IGHV
gene status and SOX11 expression were independent risk factors. In conclusion, these observations suggest the idea that MCL with mutated
IGHV
, SOX11 negativity, and non-nodal presentation correspond to a subtype of the disease with more indolent behavior.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-12-1615</identifier><identifier>PMID: 22915760</identifier><language>eng</language><ispartof>Cancer research (Chicago, Ill.), 2012-08, Vol.72 (20), p.5307-5316</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids></links><search><creatorcontrib>Navarro, Alba</creatorcontrib><creatorcontrib>Clot, Guillem</creatorcontrib><creatorcontrib>Royo, Cristina</creatorcontrib><creatorcontrib>Jares, Pedro</creatorcontrib><creatorcontrib>Hadzidimitriou, Anastasia</creatorcontrib><creatorcontrib>Agathangelidis, Andreas</creatorcontrib><creatorcontrib>Bikos, Vasilis</creatorcontrib><creatorcontrib>Darzentas, Nikos</creatorcontrib><creatorcontrib>Papadaki, Theodora</creatorcontrib><creatorcontrib>Salaverria, Itziar</creatorcontrib><creatorcontrib>Pinyol, Magda</creatorcontrib><creatorcontrib>Puig, Xavier</creatorcontrib><creatorcontrib>Palomero, Jara</creatorcontrib><creatorcontrib>Vegliante, Maria Carmela</creatorcontrib><creatorcontrib>Amador, Virgina</creatorcontrib><creatorcontrib>Martinez-Trillos, Alejandra</creatorcontrib><creatorcontrib>Stefancikova, Lenka</creatorcontrib><creatorcontrib>Wiestner, Adrian</creatorcontrib><creatorcontrib>Wilson, Wyndham</creatorcontrib><creatorcontrib>Pott, Christiane</creatorcontrib><creatorcontrib>Calasanz, Maria Jose</creatorcontrib><creatorcontrib>Trim, Nicola</creatorcontrib><creatorcontrib>Erber, Wendy</creatorcontrib><creatorcontrib>Sander, Birgitta</creatorcontrib><creatorcontrib>Ott, German</creatorcontrib><creatorcontrib>Rosenwald, Andreas</creatorcontrib><creatorcontrib>Colomer, Dolors</creatorcontrib><creatorcontrib>Giné, Eva</creatorcontrib><creatorcontrib>Siebert, Reiner</creatorcontrib><creatorcontrib>Lopez-Guillermo, Armando</creatorcontrib><creatorcontrib>Stamatopoulos, Kostas</creatorcontrib><creatorcontrib>Beà, Sílvia</creatorcontrib><creatorcontrib>Campo, Elías</creatorcontrib><title>Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biological and clinical features</title><title>Cancer research (Chicago, Ill.)</title><description>Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive clinical course while others have an indolent behavior. We performed an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B cell receptors may identify different subsets of tumors. ‘Truly unmutated’ (100% identity)
IGHV
genes were found in 24% cases, 40% were ‘minimally/borderline mutated’ (99.9-97%), 19% ‘significantly mutated’ (96.9-95%) and 17% ‘hypermutated’ (<95%). Tumors with high (≥97%) or low (<97%) mutational load used different
IGHV
genes and their gene expression profiles were also different for several gene pathways. A gene set enrichment analysis showed that MCL with high and low
IGHV
mutations were enriched in memory and naïve B-cell signatures, respectively. Furthermore, the highly mutated tumors displayed less genomic complexity, were preferentially
SOX11
negative, and showed more frequently non-nodal disease. The best cut-off of germline identity of
IGHV
genes to predict survival was 3%. Patients with high and low mutational load had significant different outcome with 5-year overall survival of 59% and 40%, respectively (
P
=0.004). Nodal presentation and SOX11 expression also predicted for poor overall survival. In a multivariate analysis,
IGHV
gene status and SOX11 expression were independent risk factors. In conclusion, these observations suggest the idea that MCL with mutated
IGHV
, SOX11 negativity, and non-nodal presentation correspond to a subtype of the disease with more indolent behavior.</description><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqljM1KxDAcxIMobv14BOH_Al2btmm7F0EW3fWgHhTxVtL0320kH6VJF_scvrBRRPDsaWb4zQwhFzRZUsqqyyRJqpjlZbpcXz_ENI1pQdkBiSjLqrjMc3ZIot_Ogpw49xYiowk7Jos0XVFWFklEPu6tQjEpPoKbGofege1Ac-MVgkClQM166K3m0GInDbbQzOB7hLvN9gX05LmX1nAFLrjJATctPD2-Ugr4PozoXKDQ8z1CK52XRnhopFV2J0UYfbWFkuY7dBgewuSMHHVcOTz_0VNydXvzvN7Gw9RobAUaP3JVD6PUfJxry2X9lxjZ1zu7r7OyyFZZlf374BMEgnfu</recordid><startdate>20120820</startdate><enddate>20120820</enddate><creator>Navarro, Alba</creator><creator>Clot, Guillem</creator><creator>Royo, Cristina</creator><creator>Jares, Pedro</creator><creator>Hadzidimitriou, Anastasia</creator><creator>Agathangelidis, Andreas</creator><creator>Bikos, Vasilis</creator><creator>Darzentas, Nikos</creator><creator>Papadaki, Theodora</creator><creator>Salaverria, Itziar</creator><creator>Pinyol, Magda</creator><creator>Puig, Xavier</creator><creator>Palomero, Jara</creator><creator>Vegliante, Maria Carmela</creator><creator>Amador, Virgina</creator><creator>Martinez-Trillos, Alejandra</creator><creator>Stefancikova, Lenka</creator><creator>Wiestner, Adrian</creator><creator>Wilson, Wyndham</creator><creator>Pott, Christiane</creator><creator>Calasanz, Maria Jose</creator><creator>Trim, Nicola</creator><creator>Erber, Wendy</creator><creator>Sander, Birgitta</creator><creator>Ott, German</creator><creator>Rosenwald, Andreas</creator><creator>Colomer, Dolors</creator><creator>Giné, Eva</creator><creator>Siebert, Reiner</creator><creator>Lopez-Guillermo, Armando</creator><creator>Stamatopoulos, Kostas</creator><creator>Beà, Sílvia</creator><creator>Campo, Elías</creator><scope>5PM</scope></search><sort><creationdate>20120820</creationdate><title>Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biological and clinical features</title><author>Navarro, Alba ; 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We performed an integrative and multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the clonotypic B cell receptors may identify different subsets of tumors. ‘Truly unmutated’ (100% identity)
IGHV
genes were found in 24% cases, 40% were ‘minimally/borderline mutated’ (99.9-97%), 19% ‘significantly mutated’ (96.9-95%) and 17% ‘hypermutated’ (<95%). Tumors with high (≥97%) or low (<97%) mutational load used different
IGHV
genes and their gene expression profiles were also different for several gene pathways. A gene set enrichment analysis showed that MCL with high and low
IGHV
mutations were enriched in memory and naïve B-cell signatures, respectively. Furthermore, the highly mutated tumors displayed less genomic complexity, were preferentially
SOX11
negative, and showed more frequently non-nodal disease. The best cut-off of germline identity of
IGHV
genes to predict survival was 3%. Patients with high and low mutational load had significant different outcome with 5-year overall survival of 59% and 40%, respectively (
P
=0.004). Nodal presentation and SOX11 expression also predicted for poor overall survival. In a multivariate analysis,
IGHV
gene status and SOX11 expression were independent risk factors. In conclusion, these observations suggest the idea that MCL with mutated
IGHV
, SOX11 negativity, and non-nodal presentation correspond to a subtype of the disease with more indolent behavior.</abstract><pmid>22915760</pmid><doi>10.1158/0008-5472.CAN-12-1615</doi></addata></record> |
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| source | American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| title | Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biological and clinical features |
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