AACR 2017 | Poster 1318/19 – Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma genome-wide association study finds an association with chromosomes 6 and 14

On Monday 3^rd April, during the American Association for Cancer Research (AACR) 2017 annual meeting, a poster (1318 / 19) by Mary L. McMaster, from NCI-DCEG, Bethesda, MD, et al. titled “A genome-wide association study of Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma demonstrates association with chromosomes 6 and 14” was presented.

The group aimed to find common genetic aberrations resulting in susceptibility to Waldenström Macroglobulinemia (WM). They carried out a two-stage Genome-Wide Association study (GWAS) which included more than 450 WM cases and 4,300 controls of European ancestry. Stage 1 (discovery) included 217 cases of WM (40% familial) and 3,798 controls. Stage 2 (replication) included 269 WM or LPL cases (4% familial) and 571 controls.

Key Highlights:

• Two novel loci on chromosomes 6 and 14 associated with WM/LPL
• Stage 1 set enriched for familial cases, and strongest signals replicated in mostly non-familial dataset
• Preliminary results confirm replication of the chromosome 6 locus
• EXOC2, the strongest signal (chromosome 6), is associated with DLBCL; common genetic mechanisms potentially contribute to development of heterogeneous Lymphoma subsets
• Chromosome 14 signal found in intergenic region near T-Cell Leukemia (TCL) gene family
  • TCL1A is potential candidate; expression is differentiation stage-specific in B-cells and is aberrantly expressed in mature B-cell malignancies including WM

The poster was concluded by stating that this group’s results provide some understanding of the underlying genetic basis of WM susceptibility.