The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis.

@article{Hunter2014TheGL,
  title={The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis.},
  author={Zachary R. Hunter and Lian Xu and Guocai Yang and Yangsheng Zhou and Xia Liu and Yanglin Cao and Robert J. Manning and Christina K. Tripsas and Christopher J. Patterson and Patricia Sheehy and Steven P P Treon},
  journal={Blood},
  year={2014},
  volume={123 11},
  pages={
          1637-46
        }
}
The genetic basis for Waldenström macroglobulinemia (WM) remains to be clarified. Although 6q losses are commonly present, recurring gene losses in this region remain to be defined. We therefore performed whole genome sequencing (WGS) in 30 WM patients, which included germline/tumor sequencing for 10 patients. Validated somatic mutations occurring in >10% of patients included MYD88, CXCR4, and ARID1A that were present in 90%, 27%, and 17% of patients, respectively, and included the activating… Expand
Clinical Validation of a CXCR4 Mutation Screening Assay for Waldenstrom Macroglobulinemia.
TLDR
A set of clinical assays to detect mutations in CXCR4 mutations in a clinical laboratory successfully validated and designed and validated Sanger sequencing and pyrosequencing assays and identified a novel missense variant and a previously reported variant of uncertain clinical significance. Expand
Genomic Landscape of Waldenström Macroglobulinemia and Its Impact on Treatment Strategies.
  • S. Treon, Lian Xu, +21 authors J. Castillo
  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2020
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM), including MYD88 (95%-97%), CXCR4 (30%-40%), ARID1A (17%), and CD79B (8%-15%). DeletionsExpand
Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia.
TLDR
Targeted therapies directed against MYD88 and/or CXCR4 signaling may provide a personalized treatment approach to Waldenström macroglobulinemia and impact overall survival in WM. Expand
Genetic and Signaling Abnormalities in Waldenstrom’s Macroglobulinemia
The genomic alterations that drive the signaling of Waldenstrom’s macroglobulinemia distinguish it from related malignancies such as marginal zone lymphoma, chronic lymphocytic leukemia, and IgMExpand
Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia.
Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%),Expand
Genomic Landscape of CXCR4 Mutations in Waldenström Macroglobulinemia
TLDR
A specific signature associated to CXCR4mut is identified, characterized with complex genomic aberrations among MYD88L265P Waldenström macroglobulinemia. Expand
CXCR4 mutations affect presentation and outcomes in patients with Waldenström macroglobulinemia: A systematic review
TLDR
A systematic review shows that Waldenström macroglobulinemia patients with CXCR4MUT have specific clinical features and have lower response and PFS rates to BTK inhibitors, and support standardization of CxCR4 testing and development of CX CR4-directed therapy. Expand
Pattern of somatic mutations in patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance
TLDR
Waldenström macroglobulinemia patients with wild-type MYD88 had a distinct clinical phenotype characterized by less bone marrow infiltration and more frequent extramedullary involvement compared to patients with mutated MyD88, which indicated that CXCR4 mutations were present in the dominant clone in the majority of cases. Expand
Waldenström macroglobulinemia: biology, genetics, and therapy
TLDR
The present pathophysiologic understanding of WM is reviewed in light of the recent MYD88 and CXCR4 discovery, as well as current and emergent treatment regimens with focus on ibrutinib. Expand
MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia
TLDR
MyD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease‐defining feature in WM, and the findings warrant external validation. Expand
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