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- Stéphanie Poulain
- 1Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France.
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- Christophe Roumier
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Aurélie Venet-Caillault
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Martin Figeac
- 4IFR114, Plateforme de Génomique, Lille, France.
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- Charles Herbaux
- 3INSERM UMR 1172, IRCL, Lille, France.
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- Guillemette Marot
- 6Université de Lille, UDSL, EA2694 Biostatistics/Inria Lille Nord Europe, MODAL, Lille, France.
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- Emmanuelle Doye
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Elisabeth Bertrand
- 3INSERM UMR 1172, IRCL, Lille, France.
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- Sandrine Geffroy
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Frédéric Lepretre
- 4IFR114, Plateforme de Génomique, Lille, France.
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- Olivier Nibourel
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Audrey Decambron
- 1Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France.
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- Eileen Mary Boyle
- 3INSERM UMR 1172, IRCL, Lille, France.
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- Aline Renneville
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Sabine Tricot
- 1Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France.
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- Agnès Daudignon
- 1Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France.
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- Bruno Quesnel
- 3INSERM UMR 1172, IRCL, Lille, France.
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- Patrick Duthilleul
- 1Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, France.
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- Claude Preudhomme
- 2Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
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- Xavier Leleu
- 3INSERM UMR 1172, IRCL, Lille, France.
説明
<jats:title>Abstract</jats:title> <jats:p>Purpose: Whole-genome sequencing has revealed MYD88 L265P and CXCR4 mutations (CXCR4mut) as the most prevalent somatic mutations in Waldenström macroglobulinemia. CXCR4 mutation has proved to be of critical importance in Waldenström macroglobulinemia, in part due to its role as a mechanism of resistance to several agents. We have therefore sought to unravel the different aspects of CXCR4 mutations in Waldenström macroglobulinemia.</jats:p> <jats:p>Experimental Design: We have scanned the two coding exons of CXCR4 in Waldenström macroglobulinemia using deep next-generation sequencing and Sanger sequencing in 98 patients with Waldenström macroglobulinemia and correlated with SNP array landscape and mutational spectrum of eight candidate genes involved in TLR, RAS, and BCR pathway in an integrative study.</jats:p> <jats:p>Results: We found all mutations to be heterozygous, somatic, and located in the C-terminal domain of CXCR4 in 25% of the Waldenström macroglobulinemia. CXCR4 mutations led to a truncated receptor protein associated with a higher expression of CXCR4. CXCR4 mutations pertain to the same clone as to MYD88 L265P mutations but were mutually exclusive to CD79A/CD79B mutations (BCR pathway). We identified a genomic signature in CXCR4mut Waldenström macroglobulinemia traducing a more complex genome. CXCR4 mutations were also associated with gain of chromosome 4, gain of Xq, and deletion 6q.</jats:p> <jats:p>Conclusions: Our study panned out new CXCR4 mutations in Waldenström macroglobulinemia and identified a specific signature associated to CXCR4mut, characterized with complex genomic aberrations among MYD88L265P Waldenström macroglobulinemia. Our results suggest the existence of various genomic subgroups in Waldenström macroglobulinemia. Clin Cancer Res; 22(6); 1480–8. ©2015 AACR.</jats:p>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 22 (6), 1480-1488, 2016-03-14
American Association for Cancer Research (AACR)