American Association for Cancer Research
10780432ccr150646-sup-143098_1_supp_3081437_nsnsc4.doc (68 kB)

Supplemental Table 1 Gene expression profilling from Genomic Landscape of CXCR4 Mutations in Waldenström Macroglobulinemia

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journal contribution
posted on 2023-03-31, 18:49 authored by Stéphanie Poulain, Christophe Roumier, Aurélie Venet-Caillault, Martin Figeac, Charles Herbaux, Guillemette Marot, Emmanuelle Doye, Elisabeth Bertrand, Sandrine Geffroy, Frédéric Lepretre, Olivier Nibourel, Audrey Decambron, Eileen Mary Boyle, Aline Renneville, Sabine Tricot, Agnès Daudignon, Bruno Quesnel, Patrick Duthilleul, Claude Preudhomme, Xavier Leleu

Gene expression profilling : List of deregulated gene identified by gene expression profilling using U133 Plus 2.0 arrays (Affymetrix, USA)


Comité Septentrion de la Ligue contre le Cancer et la Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFRMG)



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.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.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.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.

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