Title :

Genomic landscape of cxcr4 mutations in waldenstrom macroglobulinemia

Author(s) :

Poulain, Stephanie [Auteur]
Roumier, Christophe [Auteur]

Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Venet-Caillault, Aurelie [Auteur]
Figeac, Martin [Auteur]
Plateforme de génomique fonctionnelle et structurelle [Lille]
Herbaux, Charles [Auteur]
Marot, Guillemette [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Doye, Emmanuelle [Auteur]
Bertrand, Elisabeth [Auteur]
Geffroy, Sandrine [Auteur]
Leprêtre, Frédéric [Auteur]
Plateforme de génomique fonctionnelle et structurelle [Lille]
Nibourel, Olivier [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172

Decambron, Audrey [Auteur]
Boyle, Eileen Mary [Auteur]
Renneville, Aline [Auteur]
Tricot, Sabine [Auteur]
Daudignon, Agnes [Auteur]
Quesnel, Bruno [Auteur]

Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Duthilleul, Patrick [Auteur]
Preudhomme, Claude [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172

Leleu, Xavier [Auteur]

Journal title :

Clinical cancer research . an official journal of the American Association for Cancer Research

Abbreviated title :

Clin. Cancer Res.

Volume number :

22

Pages :

1480-1488

Publication date :

2016-03-15

ISSN :

1078-0432

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: Whole-genome sequencing has revealed MYD88 L265P and CXCR4 mutations (CXCR4(mut)) as the most prevalent somatic mutations in Waldenström macroglobulinemia. CXCR4 mutation has proved to be of critical importance ...
Show more >OBJECTIVE: Whole-genome sequencing has revealed MYD88 L265P and CXCR4 mutations (CXCR4(mut)) 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. METHODS: 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. 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 CXCR4(mut) Waldenström macroglobulinemia traducing a more complex genome. CXCR4 mutations were also associated with gain of chromosome 4, gain of Xq, and deletion 6q. CONCLUSIONS: Our study panned out new CXCR4 mutations in Waldenström macroglobulinemia and identified a specific signature associated to CXCR4(mut), characterized with complex genomic aberrations among MYD88L265P Waldenström macroglobulinemia. Our results suggest the existence of various genomic subgroups in Waldenström macroglobulinemia.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2019-12-09T16:52:54Z
2021-06-08T12:04:39Z